Oligosaccharide elicitors in plant immunity: Molecular mechanisms and disease resistance strategies

Abstract

The recognition of oligosaccharide elicitors, which originate from both pathogens and hosts, by membrane-localized receptors is of fundamental importance for triggering host immunity and disease resistance. It is therefore a topic of utmost significance for agricultural and botanical research. This review provides a comprehensive analysis of our current understanding of the types of oligosaccharide elicitors. We explore their diverse immunological functions, aiming to uncover the underlying mechanisms. We then detail the known recognition receptors for these oligosaccharide elicitors and describe the immune signaling pathways in which they participate. We outline the counter-defense strategies used by pathogens in response to oligosaccharide-induced immunity, offering insight into the complex interactions between plants and pathogens. Finally, we discuss challenges and limitations in the field of oligosaccharide-based immunity and propose directions for future research. A holistic view of oligosaccharide elicitors can facilitate the development of more effective strategies for enhancing plant disease resistance by leveraging mechanisms of oligosaccharide-induced immunity, ultimately promoting more sustainable agricultural practices and a better understanding of plant–pathogen interactions.

This review examines how oligosaccharide elicitors derived from pathogens and plants activate immune responses through membrane-localized receptors, detailing their types, functions, and signaling pathways. It also explores pathogen counter-defense strategies and co-evolutionary dynamics, and discusses current challenges and future directions for developing sustainable disease resistance strategies in agriculture.

Introduction

By 2100, addressing global food production will become imperative for satisfying the demands of a burgeoning population that is projected to reach ∼10.9 billion (Ioannou et al., 2020; Mahapatra et al., 2022). Sustainable crop management hinges upon a comprehensive understanding of plant defense mechanisms. Plant diseases account for approximately 30% of annual losses in crop production (Kongala and Kondreddy, 2023), highlighting the importance of these mechanisms. To protect themselves against potentially harmful microbes, plants have evolved a complex and multi-faceted innate immune system. This system involves two main receptor types: plasma-membrane-localized pattern recognition receptors (PRRs) and intracellular immune receptors. PRRs are highly sensitive to conserved microbe-associated molecular patterns (MAMPs) or plant-derived damage-associated molecular patterns (DAMPs), which trigger pattern-triggered immunity (PTI) (Jones and Dangl, 2006). The cell-wall polysaccharides of both plants and microbes serve as extracellular sources for the production of DAMPs and MAMPs (Zhou and Zhang, 2020; Kongala and Kondreddy, 2023). These molecular patterns can be released through the action of cell-wall-degrading enzymes (CWDEs) that are secreted by the invading pathogens or by the plants themselves as part of their defense response (Kubicek et al., 2014; Drula et al., 2022).

The plant cell wall, composed of polysaccharides like cellulose, hemicellulose, and pectin, serves as an effective physical barrier against microbial pathogens (Cai et al., 2022; Delmer et al., 2024). When microbial CWDEs act on glycans of the plant cell wall, hydrolysis occurs, releasing various oligosaccharides. These oligosaccharides, derived from larger polysaccharides, exhibit linear or branched structures and are composed of D-monosaccharides (e.g., glucose [Glc], xylose [Xyl], and arabinose [Ara]), typically linked by β-1,4, β-1,3, or α-1,4 bonds (Klarzynski et al., 2000; Aziz et al., 2007; Rebaque et al., 2021). Notably, the parent polysaccharides have often undergone biochemical modifications (e.g., acetylation, methylation, and esterification) that influence oligosaccharide structure and function. For example, acetylated or methylesterified residues in pectin can alter how CWDEs hydrolyze polysaccharides, shaping the composition of the released oligosaccharides (Voxeur et al., 2019; Zang et al., 2019). This complexity, rooted in both glycosidic linkages and chemical modifications, renders plant cell-wall-derived oligosaccharides diverse in structure and function. Unbranched mixed-linked glucans (MLGs) such as β-1,4-D-(Glc)2-β-1,3-D-Glc (MLG43) are found not only in plant cell walls but also in those of oomycetes and microbes (Pettolino et al., 2009; Pérez-Mendoza et al., 2015; Rebaque et al., 2021; Yang et al., 2021). Furthermore, certain plant storage oligosaccharides that are absent from cell walls, such as fructooligosaccharides derived from fructans, can be perceived by plant cells and initiate immune responses (Dobrange et al., 2019; Benkeblia, 2020). In addition to those from terrestrial plants, oligosaccharides from marine plant cell-wall polysaccharides, such as alginate and fucoidan, have been shown to activate defensive responses in some plant species (Klarzynski et al., 2000; Aitouguinane et al., 2023; Wang et al., 2023a).

During plant–pathogen interactions, the cell walls and extracellular outer layers of microorganisms serve as significant sources of oligosaccharide elicitors that are perceived as MAMPs (Wanke et al., 2021; Molina et al., 2024a). For instance, chitin oligosaccharides (CTOS), linear β-1,3-glucans, β-1,3-glucans with β-1,6-glucan branches, and β-1,6-glucan oligosaccharides are released from the cell walls of fungi/oomycetes, and peptidoglycans (PGNs) and extracellular polysaccharides are released from bacteria (Klarzynski et al., 2000; Kaku et al., 2006; Aziz et al., 2007; Gust et al., 2007; Wanke et al., 2021; Tiemblo-Martín et al., 2024). These biocompatible and biodegradable oligosaccharides can trigger a complex series of signaling events within plants, including reactive oxygen species (ROS) bursts, calcium (Ca²⁺) influx, mitogen-activated protein kinase (MAPK) activation, callose deposition, and upregulation of defense-related genes (Rebaque et al., 2021; Yuan et al., 2021).

In the present review, we explore the intricate interactions between oligosaccharide elicitors and immune responses within the context of plant–microbe interactions. We first provide a comprehensive summary of the diverse oligosaccharide types that have been reported to induce plant disease resistance (Supplemental Table 1). These oligosaccharides, with their unique structures and properties, play a crucial role in modulating plant defense mechanisms. We next focus on the recognition receptors and complex immune signal transduction pathways associated with reported oligosaccharide activators. Understanding these molecular components and the signaling cascades they initiate is fundamental to deciphering how plants perceive and respond to oligosaccharide-mediated immune stimuli. We then discuss the strategies deployed by pathogens to counteract plant oligosaccharide-mediated immunity during plant–pathogen interactions. These counter-defense strategies add another layer of complexity to the co-evolutionary arms race between plants and microbes. Finally, we critically assess existing challenges and propose future research directions for the study of oligosaccharide-induced plant disease resistance. Understanding the complex interactions between oligosaccharides and immune responses during plant–microbe interactions can facilitate sustainable agricultural development, crop improvement, and the prevention and control of plant diseases. This information can serve as a cornerstone for the development of innovative and eco-friendly agricultural practices that enhance crop productivity while minimizing the use of chemicals.

Sources of oligosaccharides as immune elicitors

Chitin oligosaccharides

Chitin, the second-most abundant natural biopolymer after cellulose, is an insoluble β-1,4-linked homopolymer of N-acetyl-D-glucosamine (GlcNAc). It is a fundamental structural component of fungal cell walls and the exoskeletons of insects, nematodes, and crustaceans (Rinaudo, 2006; Liaqat and Eltem, 2018). During plant–pathogen interactions, fungal attack triggers plants to secrete degrading proteases (e.g., chitinases and EC3.2.1.14) into the apoplastic space. These enzymes degrade chitin into bioactive fragments such as CTOS, which act as MAMPs to initiate plant immune responses (Hamel and Beaudoin, 2010; Khokhani et al., 2021; Wang et al., 2022).

CTOS are recognized by plant PRRs, initiating PTI. In rice suspension cells, CTOS induce dose- and polymerization-dependent cell death and defense gene expression (Ning et al., 2004), as well as MAPK activation and ROS production (Cao et al., 2014). Recent years have seen a growing agricultural interest in CTOS, driven by their biocompatibility, biodegradability, non-toxicity, and broad-spectrum biological activities with no reported environmental risks (Riseh et al., 2024b). Treatment with CTOS enhances resistance against fungi, oomycetes, bacteria, viruses, and nematode pathogens in diverse plant species, including crops (Ning et al., 2004; Miya et al., 2007; Gong et al., 2020; Riseh et al., 2024b). Notably, CTOS can induce plant systemic immunity: root perception of CTOS primes leaf PTI, enabling plants to mount more robust defenses against subsequent pathogen attacks. Soil amendment with CTOS has been shown to protect lettuce, tomato, and Arabidopsis against Pseudomonas syringae pv. tomato DC3000 (Pst) and wheat against Blumeria graminis (powdery mildew) (Makechemu et al., 2024).

Chitosan oligosaccharides

Chitosan, the deacetylated product of chitin, is a linear polysaccharide composed of β-(1,4)-linked D-glucosamine. Chitosan oligosaccharides (CSOS), the primary degradation products of chitosan generated by chemical hydrolysis or enzymatic degradation, are fully water soluble owing to their shorter chain lengths and the free amino groups in their D-glucosamine residues. CSOS have been used extensively across diverse fields because of their low molecular weights, non-toxicity, rapid absorption, and stable biocompatibility (Guan and Feng, 2022). In agriculture, CSOS serve as potent plant immune activators for the eco-friendly control of plant diseases. For instance, CSOS induce dose-dependent cell death in tobacco cells, accompanied by H₂O₂ accumulation through CSOS-mediated apoptosis-like cell death independent of the H₂O₂ signaling pathway (Wang et al., 2008). In Arabidopsis and tobacco, CSOS activate the salicylic acid (SA) and Ca²⁺ signaling pathways, respectively, to enhance resistance against tobacco mosaic virus (TMV) (Lu et al., 2010; Jia et al., 2016). In addition, CSOS enhance the resistance of carrot to Sclerotinia sclerotiorum (Molloy et al., 2004), potato to Phytophthora infestans (Huang et al., 2021), tomato to Phytophthora nicotianae (González-Peña Fundora et al., 2022), and camellia to Colletotrichum camelliae (Li and Zhu, 2013). CSOS can mitigate abiotic as well as biotic stresses. For example, CSOS enhance the tolerance of edible rape (Brassica rapa L.) to cadmium (Cd) by promoting antioxidant enzyme activities and altering the subcellular distribution of Cd (Zong et al., 2017).

CSOS can also synergize with other compounds to amplify the induction effect. Binary mixtures of CSOS–propolis and CSOS–silver nanoparticles exhibit potent antifungal activity against Fusarium circinatum and Diplodia pinea, respectively, reducing their mycelial growth by approximately 80% (Silva-Castro et al., 2018). Combined biofungicides like ε-poly-L-lysine + CSOS combine direct antifungal activity against Botrytis cinerea with the induction of plant resistance, positioning them as promising biocontrol agents (Sun et al., 2018). The cytosinpeptidemycin–CSOS complex triggers ROS production and upregulates defense-responsive genes (PR1, PR5, FLS2, and Hsp70) while inducing TMV resistance in Nicotiana glutinosa (Guo et al., 2020). Collectively, these findings demonstrate that CSOS-based complexes can serve as versatile plant immune activators and eco-friendly fungicides for integrated disease management.

Pectin oligosaccharides

Pectins, a class of acidic polysaccharides, are fundamental components of the plant cell-wall matrix, maintaining integrity and intercellular cohesion, and serving as immune signaling regulators. The pectin matrix consists of three major polysaccharides: homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) (Riseh et al., 2024a; Anderson and Pelloux, 2025). HG—a linear polymer of α-1,4-linked galacturonic acid (GalA) residues, methylesterified at C6 and often acetylated at C2/C3 (Mohnen, 2008; Anderson, 2016)—is the principal precursor of immunogenic pectin-derived oligosaccharides (POSs), whereas RG-I features an α-D-GalA-(1,2)-α-L-Rha backbone, and RG-II contains GalA with diverse sugar moieties (Ridley et al., 2001).

HG can be degraded by a series of CWDEs, including polygalacturonase (PG; EC 3.2.1.15), pectin methylesterase (PME; EC 3.1.1.11), pectate lyases (PELs; EC 4.2.2.2), and pectin lyases (PLs; EC 4.2.2.10, EC 4.2.2.2) (Blackman et al., 2014). Specifically, PLs degrade HG via β-elimination to generate POSs with diverse methylesterified and acetylated modifications. Concurrently, PME catalyzes the cleavage of methyl ester groups in HG, de-esterifying the polymer and facilitating PG-mediated hydrolysis of α-1,4-glycosidic bonds to produce GalA oligomers (OGs). Notably, during B. cinerea infection of Arabidopsis thaliana, fungal PLs and PG account for 80% and 20% of POS production, respectively, with most POSs retaining acetyl- and methyl-esterified groups (Voxeur et al., 2019).

Pathogen-derived PGs disrupt cell-wall integrity through enzymatic activity, generating short oligogalacturonides (OG_2-7) that suppress PTI (Moerschbacher et al., 1999; Xiao et al., 2024). Plants use PG-inhibiting proteins (PGIPs) to counteract this suppression, activating defense mechanisms that drive the production of long-chain oligogalacturonides (OG_10–15) that function as DAMPs. For instance, the interaction between Phaseolus vulgaris PGIP2 (PvPGIP2) and Fusarium phyllophilum PG (FpPG) modifies FpPG, enhancing its substrate-binding activity and altering substrate preference to generate OG_10–15 (Xiao et al., 2024). The biological activity of OG_10–15 hinges on their molecular size, as the optimal length enables the formation of a Ca²⁺-mediated “egg-box” structure that is critical for the function of OGs as DAMPs (Cabrera et al., 2008; Sanabria et al., 2008; Hématy et al., 2009; Ferrari et al., 2013; Martínez-Gómez et al., 2023). During pathogen infection, OG_10–15 induce diverse defense responses, including ROS bursts, MAPK activation, callose deposition, and accumulation of phytoalexins, glucanase, and chitinase (Davis and Hahlbrock, 1987; Ferrari et al., 2013; Gust et al., 2017; Hou et al., 2019; Xiao et al., 2024). Treatment with exogenous OGs can protect plants from pathogen infection (Davidsson et al., 2017; Hou et al., 2019; Howlader et al., 2020b) and can affect post-harvest physiology by accelerating wound healing while inhibiting fruit softening via Ca²⁺ signaling and ethylene production (Denoux et al., 2008; Ferrari et al., 2013; Lu et al., 2021). However, some reports have shown that trigalacturonic acid (GalA₃) can activate plant immunity (Davidsson et al., 2017; Liu et al., 2023a; Molina et al., 2024b). We speculate that this may depend on the host background, oligosaccharide molecular structure, and experimental conditions.

PLs and PELs differ in substrate specificity. PLs cleave the α-1,4 glycosidic bonds in highly methylated or unmethylesterified pectin through a β-elimination reaction, whereas PELs act only on unmethylated pectin (Sassi et al., 2017). Both enzymes generate oligosaccharides that function as DAMPs. For example, Phytophthora sojae secretes PL PsPL1, which degrades soybean pectin into POSs with a degree of polymerization (DP) ranging from 3 to 14, as confirmed by high-performance anion-exchange chromatography with pulsed amperometric detection and liquid chromatography–mass spectrometry (Sun et al., 2024). These POSs, which feature diverse acetylation and methylation modifications, stimulate plant immunity and resistance, establishing them as DAMPs released during P. sojae infection.

In addition to the POSs released from HG, POSs dissociated from pectin branch structures can also activate plant immunity. A mixture of POSs, including oligogalacturonides and rhamnogalacturonan oligosaccharide, induced strong resistance against Pst by enhancing SA accumulation and upregulating SA-associated genes (PR1, PR2, and PR5) (Howlader et al., 2020a). Moreover, plants pretreated with these mixed POSs exhibited significant production of ROS and nitric oxide (NO), further reinforcing their role in the activation of broad-spectrum plant defense (Howlader et al., 2020a). Given the complexity of pectins from different plant sources, the functions of POSs in inducing plant resistance and mechanisms such as structure–function relationships still require in-depth study.

Cellulose oligosaccharides

Cellulose, a linear polymer of β-1,4-glucosyl residues, is found in all plants, most algae, certain protists, and the extracellular matrices or walls of microbes (including bacteria and oomycetes). It stands as the most abundant biomolecule on earth (Burton and Fincher, 2009; Kloareg et al., 2021). Comprising over 30% of the primary cell wall material, cellulose forms unbranched fibers with a paracrystalline structure.

During plant–pathogen interactions, both organisms secrete cellulases that target cellulose, generating cellulose oligosaccharides (cellooligomers). The cellooligomers released from plant cell walls by microbial cellulases act as DAMPs during pathogen colonization (Gámez-Arjona et al., 2022). The strength of the immune response triggered by cellooligomers depends on the oligomer length. For instance, cellobiose does not stimulate ROS bursts and callose deposition (Souza et al., 2017), but cellooligomers with 3–7 Glc units (CEL_3–7) trigger Ca²⁺ influx, ROS production, MAPK activation, and defense-related gene expression in Arabidopsis, rice, and other plant species, ultimately enhancing pathogen resistance (Claverie et al., 2018; Rebaque et al., 2021; Yang et al., 2021; Tseng et al., 2022; Martín-Dacal et al., 2023).

Cellooligomers derived from fungal cell walls can also act as MAMPs to activate plant immunity. Fungal cellotriose induces weak ROS production in Arabidopsis roots, but its combination with chitin triggers significantly stronger ROS production than either molecule alone (Johnson et al., 2018), demonstrating that cellotriose functions as an amplifier for PTI. In Arabidopsis, plant-derived cellobiose markedly facilitated the ability of flg22 or OGs, but not chitin, to induce an ROS burst (Souza et al., 2017). These findings demonstrate that PRRs are indispensable for the cell-wall integrity system during PTI, sensing both microbe-derived and plant-derived oligosaccharides. In addition, cellooligomers can be released during abiotic stresses (such as salt or drought) that disrupt plant cell-wall integrity and during plant developmental processes that involve cell-wall remodeling (Bacete et al., 2022; Gigli-Bisceglia et al., 2022).

Hemicellulose oligosaccharides

Hemicelluloses consist of xylans, xyloglucans, mannans, glucomannans, and β-(1,3/1,4)-glucans. Unlike cellulose, hemicelluloses have short branches and an amorphous structure, making them readily accessible to hydrolases (Scheller and Ulvskov, 2010; Gibson, 2012). The mixed-linkage β-(1,3/1,4)-glucans (MLGs), which consist of unbranched and unsubstituted chains with β-1,4-glucosyl residues interspersed with β-1,3-linkages, are representative immunogenic oligosaccharides derived from hemicellulose degradation and play a key role in plant immune signaling.

MLGs are widely distributed as matrix polysaccharides in the cell walls of Poaceae species (cereals), Equisetum spp., other vascular plants, bryophytes, and algae (Popper and Fry, 2003; Fry et al., 2008; Salmeán et al., 2017). The endoglucanases MoCel12A and MoCel12B secreted by Magnaporthe oryzae target rice cell-wall hemicellulose, releasing two specific oligosaccharides: the trisaccharide 3¹-β-D-cellobiosyl-Glc (β-1,4-D-(Glc)₂-β-1,3-D-Glc, MLG43) and the tetrasaccharide 3¹-β-D-cellotriosyl-Glc (β-1,4-D-(Glc)₃-β-1,3-D-Glc, MLG443) (Yang et al., 2021). These Poaceae-specific oligosaccharides trigger an ROS burst (Yang et al., 2021). MLG43, MLG443, and MLG34 (β-1,3-D-Glc-β-1,4-D-Glc₂) are recognized with varying degrees of specificity by the immune systems of other plant species, including Arabidopsis, Capsicum annuum (pepper), Hordeum vulgare (barley), Solanum lycopersicum (tomato), and Triticum aestivum (wheat). MLG43-mediated PTI is the most thoroughly characterized (Aziz et al., 2007; Rebaque et al., 2021, 2024; Yang et al., 2021). Plant endogenous enzymes also hydrolyze cell-wall polysaccharides. For example, a Zea mays (maize) GH17 licheninase releases MLG and other oligosaccharides (Kraemer et al., 2021). In addition, MLGs released from bacteria, fungi, and oomycetes can act as MAMPs in plant species that lack these polysaccharides in their cell walls (Fontaine et al., 2000; Pettolino et al., 2009; Pérez-Mendoza et al., 2015; Rebaque et al., 2021).

In addition to MLGs, other hemicellulose components—including xylans, xyloglucans, and mannans—also serve as precursors of immunomodulatory oligosaccharides, extending the scope of hemicellulose-derived signals in plant defense. The backbones of xylans, xyloglucans, and mannans are composed of β-(1,4)-linked monomer residues. Pathogen-secreted xylanases degrade plant cell-wall hemicellulose, releasing arabinoxylan oligosaccharides such as 3³-α-L-arabinofuranosyl-xylotetraose (XA₃XX) as DAMPs. These oligosaccharides have highly bioactive structures that trigger robust immune responses in Arabidopsis and enhance crop disease resistance (Claverie et al., 2018; Mélida et al., 2020). Linear xylan oligosaccharides (β-1,4-D-(Xyl)_2-5, XYL_2-5) are recognized with varying degrees of specificity by plant immune systems, inducing defense-related responses and modifications of cell-wall composition (Dewangan et al., 2023; Pring et al., 2023; Fernández-Calvo et al., 2024). Notably, XYL₄ exhibits weaker PTI induction than XA₃XX, which has an Ara substituent at the 3-position (Mélida et al., 2020). A. thaliana can also detect plant-derived glucuronoxylan oligosaccharides such as 2³–(4-O-methyl-α-D-glucuronyl)-xylotetraose (XUXX) (Fernández-Calvo et al., 2024). In addition, mannan oligosaccharides trigger multiple defense responses against P. nicotianae and Xanthomonas oryzae in tobacco and rice, including Ca²⁺ accumulation, MAPK activation, ROS bursts, and activation of jasmonic acid- and SA-dependent defense signaling pathways (Zang et al., 2019). Konjac glucomannan oligosaccharides (KGMOS) consist primarily of Glc and mannose residues linked by β-1,4-glycosidic bonds, and pretreatment with KGMOS, particularly at a low concentration (25 mg/L), induced resistance against P. nicotianae in plants (Rajib et al., 2024).

Algae oligosaccharides

Alginate is a linear copolymer of (1,4)-linked β-D-mannuronate (M) and its C-5 epimer, α-L-guluronate (G). These monomers are arranged in diverse sequences, forming homopolymeric M-blocks (PolyM), homopolymeric G-blocks (PolyG), or heteropolymeric MG-blocks (PolyMG) (Aitouguinane et al., 2020, 2023). As the most abundant polysaccharide in brown algae, comprising up to 40% of algal dry matter, alginate is harvested primarily for applications in medicine, food science, and agriculture (Bose et al., 2019; Han et al., 2019). Alginate lyases are key enzymes for the production of alginate oligosaccharides (AOSs), which are functional oligosaccharides composed of 2–20 M/G units and low-molecular-weight alginates. These enzymes degrade alginate by β-elimination at the non-reducing end (Wong et al., 2000; Sim et al., 2017). For example, alginate lyase Alg7A derived from Vibrio sp. W1, which was characterized by thin-layer chromatography and ESI–MS, preferentially released trisaccharides from alginate, highlighting its potential for AOS production (Zhu et al., 2019).

The biological activity of AOSs is tightly linked to their DP and structure (Zhang et al., 2020). For example, the disaccharide ΔG strongly induces glyceollin biosynthesis in soybean seeds (Peng et al., 2018). Low-molecular-weight alginates trigger defense responses in diverse plant species through SA-mediated signaling pathways (Zhang et al., 2019; Aitouguinane et al., 2020, 2023), upregulating defense marker genes such as PAL (phenylalanine ammonia-lyase), PR1 (pathogenesis-related protein 1), SOD (superoxide dismutase), and DHN (dehydrin) (Drira et al., 2023). Although AOSs show promise in biotechnological applications, their structural characterization remains challenging owing to their compositional complexity and heterogeneity (Jutur et al., 2016).

Fucoidans from brown marine algae are polysaccharides composed predominantly of sulfated L-fucoses (Klarzynski et al., 2000; Wang et al., 2023a). A. thaliana can perceive glycan structures containing diverse monosaccharides, including L-fucose in fucoidans and D-mannuronic acid and L-guluronic acid in alginates (Galletti et al., 2008; Voxeur et al., 2019; Aitouguinane et al., 2023). The unbranched β-1,3-glucans laminarin and laminarihexaose (β-1,3-(Glc)₆) trigger robust immune responses in H. vulgare (barley) and Brachypodium distachyon (Wanke et al., 2020). In the dicot Nicotiana benthamiana, laminarin elicits strong immune responses, whereas laminarihexaose induces a weaker Ca²⁺ influx and ROS burst (Wanke et al., 2020).

Carrageenans are gel-forming linear sulfated galactans extracted from red marine algae, composed of D-galactose residues with alternating α-1,3- and β-1,4-linkages. They are classified into three main types based on sulfate substitution patterns and the 3,6-anhydro bridge in α-l,4-linked galactose: κ-carrageenan (3,6-anhydro-α-D-galactopyranosyl-1,4-4-sulfate-β-D-galactose), ι-carrageenan (2-sulfate-3,6-anhydro-α-D-galactopyranosyl-1,4-4-sulfate-β-D-galactose), and λ-carrageenan (2,6-sulfate-α-D-galactopyranosyl-1,4-2-sulfate-β-D-galactose). Among these, the κ-carrageenase Car19 hydrolysate protects cucumber plants against cucumber mosaic virus by suppressing virus replication and enhancing antioxidant enzyme activity in infected tissues (Li et al., 2019).

Agaro-oligosaccharides (AOs) are the degradation products of agar, a red algae cell-wall component, classified on the basis of their cleavage sites into agaroligosaccharides (reducing ends: β-D-galactose) and neoagarooligosaccharides (3,6-endo-α-L-galactose). According to their cleavage sites, AOs induce disease resistance in peach fruit by activating antioxidant and phenylpropanoid metabolism pathways (Kang et al., 2014; Chen et al., 2021; Li et al., 2024).

Other oligosaccharides

Glucans have emerged as key players in PTI, and in addition to cellooligomers and hemicellulose oligosaccharides, other glucans can also activate plant immunity. For example, β-1,2-glucan trisaccharide (B2G3) can trigger ROS production, MAPK phosphorylation, and differential expression of defense-related genes in Arabidopsis, maize, and wheat. Pretreatments with B2G3 improved these plants’ defense against fungal infections (Fuertes-Rabanal et al., 2024). Curdlan, a linear water-insoluble β-1,3-glucan produced by Agrobacterium sp. fermentation, is approved as a safe food additive (Spicer et al., 1999). Pretreatment of potato plants with curdlan oligosaccharide 1 day before P. infestans infection significantly reduced the lesion area on potato leaves (Li et al., 2014). Interestingly, the perception of short and long β-1,3-glucans differs among plant species. The leaves of N. benthamiana activate immunity in response to long β-1,3-glucans, whereas A. thaliana and Capsella rubella perceive short β-1,3-glucans (Wanke et al., 2020), suggesting that the structural complexity of β-glucans contributes to differences in their recognition by plant species. One insufficiently studied type of β-glucan is pustulan (β-1,6-glucan), which can trigger a weak Ca²⁺ burst and MAPK activity in A. thaliana (Fernández-Calvo et al., 2024). In addition, A. thaliana can perceive α-1,4-glucan-derived oligosaccharides such as α-D-maltotetraose (MAL₄) to trigger plant immune responses (Fernández-Calvo et al., 2024), and bacteria can differentially recognize and respond to α-1,4-D-glucans and cellooligomers by triggering distinct genome-wide transcriptional responses that have antagonistic effects on bacterial motility (Bonfim et al., 2023; Molina et al., 2024b).

Pullulan is produced by Aureobasidium pullulans as an amorphous slime material consisting of maltotriose repeating units joined by α-1,6 linkages. Application of pullulan shows potential for the control of postharvest soft rot in kiwifruit, offering an effective strategy for enhancing storage stability and shelf life of this economically important fruit (Yu et al., 2024).

Burdock fructooligosaccharide (BFO), a natural elicitor isolated from Arcitum lappa root, is a linear chain of 12 β-(2,1)-linked fructofuranose residues with a single terminal α-(1,2)-linked glucopyranose unit. It shows significant potential as an elicitor for control of postharvest fruit disease. BFO induces the upregulation of NPR1, PR1, PAL, and STS genes; inhibits declines in total phenol content; and activates chitinase and β-1,3-glucanase enzymes (Sun et al., 2013). By triggering the SA-dependent signaling pathway, BFO suppresses postharvest browning in Kyoho grapes. It also enhances the resistance of tomatoes to B. cinerea (He et al., 2006; Wang et al., 2009), cucumbers to Colletotrichum orbiculare (Zhang et al., 2009), and tobacco to TMV (Wang et al., 2009). Mechanistically, BFO-induced stomatal closure is mediated by ROS and ROS-dependent NO production (Guo et al., 2013).

Oligosaccharide perception and immune signaling

Diverse oligosaccharide ligands derived from plant or microbial cell walls that vary in biochemical composition and structure are detected by the plant immune system via the extracellular ectodomains (ECDs) of PRRs. This recognition initiates the formation of oligosaccharide ligand–PRR complexes and activates PTI. However, the intricate structures of oligosaccharides pose significant challenges to their purification and separation, hindering efforts to investigate their mechanisms of action. Our understanding of how oligosaccharide ligands activate plant defenses lags behind that of peptide ligand recognition by PRRs (Bacete et al., 2018). The molecular mechanisms of oligosaccharide perception in plants remain poorly characterized, with only a limited number of PRRs and co-PRRs identified to date. Characterized PRRs involved in oligosaccharide recognition include lysin-motif receptor kinases (LysM RKs), which recognize chitin and PGNs (Kaku et al., 2006; Wan et al., 2019; Yang et al., 2021; Dodds et al., 2024); leucine-rich repeat-malectin (LRR-MAL) RKs, which are implicated in perception of cell-wall glycans (Fernández-Calvo et al., 2024); wall-associated kinases (WAKs), which are proposed to monitor cell-wall integrity and respond to DAMPs (Kohorn, 2016; Yao et al., 2025); and malectin-like proteins and lectin RKs, which bind diverse carbohydrate structures (Brutus et al., 2010). There are few published crystal structures of PRR ECDs, with structures resolved for only a few receptors (Liu et al., 2012; Gysel et al., 2021; Xu et al., 2023). Notably, most of these structures lack bound ligands in their binding pockets, highlighting technical challenges in capturing dynamic oligosaccharide–PRR interactions. Deciphering these mechanisms is critical for understanding plant immunity and developing targeted strategies to enhance disease resistance.

Chitin oligosaccharides perception and signaling

The mechanisms underlying chitin perception and signaling in plants were first characterized in rice (Oryza sativa) through the identification of CHITIN-ELICITOR BINDING PROTEIN (CEBiP). This protein contains three extracellular LysM motifs and a cysteine-rich domain anchored to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor (Kaku et al., 2006; Gong et al., 2020). Chitin binding induces minimal conformational changes in OsCEBiP. Structural modeling indicates that hexachitin mediates OsCEBiP homodimerization, with each LysM2 engaging three N-acetylglucosamine (NAG) units in a sliding mode (Liu et al., 2016). Molecular interaction studies between CEBiP and CTOS revealed that Ile 122 within the central LysM motif is critical for ligand binding (Hayafune et al., 2014). OsCEBiP homodimers, whose formation is mediated by chitin perception, recruit two molecules of LysM-RK CHITIN ELICITOR RECEPTOR KINASE 1 (OsCERK1), forming a heterocomplex (Figure 1A) (Hayafune et al., 2014). OsCERK1 is indispensable for chitin-induced signaling in rice and directly binds chitin hexamers ((NAG)₆) and tetramers ((NAG)₄) (Xu et al., 2023), albeit with significantly lower affinity than OsCEBiP (Liu et al., 2016). Notably, soil amendment with chitin elicits systemic disease resistance in rice, a phenomenon contingent upon the chitin receptors OsCERK1 and OsCEBiP (Makechemu et al., 2024).

Figure 1.

Immune signaling pathway of microbe-derived oligosaccharides.

(A) In rice, OsCEBiP serves as the initial sensor for CTOS and then binds to OsCERK1 to form a characteristic “sandwich”-like structure. OsLYP4 and OsLYP6 can recognize peptidoglycans (PGNs) and recruit the coreceptor OsCERK1 to form a heteromeric complex. As a coreceptor, OsCERK1 plays a pivotal role in activating downstream immune responses through multiple distinct pathways. OsCERK1 can phosphorylate OsGEF1, which, in turn, activates OsRAC1. The activation of OsRAC1 triggers the production of reactive oxygen species (ROS). In addition, OsCERK1 phosphorylates the intracellular receptor-like kinase OsRLCK185 or OsRLCK176, leading to activation of downstream immune responses such as ROS bursts, MAPK activation, and Ca²⁺ influx. Within the cytoplasm, several proteins modulate the kinase activity of OsRLCK176. For example, OsCPK17 (calcium-dependent protein kinase 17) and OsCPK4 can regulate OsRLCK176, fine-tuning the immune response. Moreover, E3 ubiquitin ligases such as OsPUB12 are involved in regulating the protein homeostasis of RLCKs, ensuring the proper functioning and turnover of these crucial immune-related proteins.

(B) In Arabidopsis thaliana, CTOS is recognized by AtLYK5 and then forms a protein complex with AtCERK1. AtCERK1, as a co-receptor, is responsible for transducing intracellular immune signals. AtCERK1 binds to and phosphorylates members of the AtRLCK VⅡ family, including AtPBL27, AtPBL19, and AtBIK1. This phosphorylation event sets in motion two distinct MAPK cascade pathways. One is the MAPKKK3/5–MKK4/5–MPK3/6 pathway, and the other is the MEKK–MKK1/2–MPK4 pathway. These MAPK cascades are essential for propagation of the immune signal and activation of various defense-related genes. AtRLCK VⅡ can phosphorylate AtRBOHD, which is a key enzyme for the production of ROS. AtCERK1 can activate Ca²⁺ influx by phosphorylating AtBIK1 and further phosphorylating AtCNGC2/4 (cyclic nucleotide-gated ion channels 2/4). AtPBL27 can phosphorylate the S-type anion channel protein AtSLAH3 to induce stomatal closure. AtPBL19 can be translocated from the cytoplasm to the nucleus under the conditions of immune activation. AtntPBL19 cleaved by metacaspase can phosphorylate EDS1 to further activate ETI. AtBAK1 can phosphorylate the juxtamembrane domain of AtCERK1, keeping AtCERK1 in a priming state and thus activating stronger fungal resistance. Chitin and chitosan induce plant resistance through different signaling pathways. CTOS can induce stomatal closure through AtCERK1, whereas CSOS induces guard-cell death through an as-yet-unknown receptor.

The chitin signaling pathway is orchestrated by a dynamic network of membrane-resident proteins, ensuring precise activation of immune responses to pathogens such as M. oryzae. Central to this process is the small GTPase OsRac1, whose activation is regulated by the guanine nucleotide exchange factor OsRacGEF1. OsRacGEF1 interacts with the chitin receptor OsCERK1 and endoplasmic reticulum (ER) chaperones to form a complex that is trafficked to the plasma membrane (PM). At the PM, OsRacGEF1 combines with OsRac1 to assemble the defensome complex, a key signaling hub for chitin responses (Akamatsu et al., 2013). Upon chitin binding, OsCERK1 phosphorylates the C-terminal serine residue of OsRacGEF1 at position 549 (S549), triggering OsRac1 activation. Activated OsRac1 is indispensable for chitin-induced ROS production, defense gene expression, and resistance to rice blast infection (Akamatsu et al., 2013). This highlights the critical role of post-translational modifications (PTMs) in the activation of signaling cascades.

The lysin motif-containing proteins OsLYP4 and OsLYP6 act as co-receptors for OsCERK1, but their association varies with ligand type (Ao et al., 2014). OsCERK1 forms heterocomplexes exclusively with OsLYP4 or OsLYP6 in the presence of PGN, whereas OsCERK1 can associate with OsLYP4, OsLYP6, or the chitin-binding protein OsCEBiP in response to chitin (Ao et al., 2014). This ligand-dependent assembly of receptor complexes underscores the pathway’s versatility in distinguishing between bacterial (PGN) and fungal (chitin) MAMPs.

OsCERK1 initiates intracellular signaling by phosphorylating the receptor-like cytoplasmic kinase OsRLCK185 in a chitin-dependent manner. OsRLCK185 activation is essential for ROS production, defense gene expression, and MAPK activation (Yamaguchi et al., 2013). Mutants that lack OsRLCK185 exhibit impaired PTI responses, confirming the role of OsRLCK185 as a central signaling node (Yamaguchi et al., 2013). Once pattern recognition occurs, OsCERK1 and OsRLCK185 are activated, leading to phosphorylation and enhancement of OsCNGC9 channel activity (Wang et al., 2019). The OsCNGC9-mediated Ca²⁺ influx initiates a series of immune responses, including the ROS burst and the expression of PTI-related defense genes. OsRLCK185 also transmits immune signaling from OsCERK1 to an MAPK signaling cascade by interacting with and phosphorylating MAPK kinases such as OsMAPKKKε, OsMAPKKK11, or OsMAPKKK18 (Wang et al., 2017; Yamada et al., 2017). This activates a downstream MAPK cascade composed of OsMAPKKKε/OsMAPKKK18–OsMKK4–OsMPK3/6 (Wang et al., 2017; Yamada et al., 2017). Another receptor-like cytoplasmic kinase, OsRLCK176, dissociates from OsCERK1 in response to both PGN and chitin treatments and regulates multiple defense responses triggered by these ligands (Ao et al., 2014), suggesting that OsRLCK176 acts downstream of OsCERK1 in the PGN and chitin signaling pathways. There is positive crosstalk between the immune signaling mediated by Ca²⁺-dependent protein kinase (CDPK) and by the receptor-like cytoplasmic kinase RLCK176, which is crucial for the maintenance of rice immune homeostasis. Rice OsCPK17 interacts with and stabilizes OsRLCK176 by phosphorylating it at Ser83. This modification prevents ubiquitination of OsRLCK176 by the U-box E3 ligase OsPUB12, thereby enhancing its stability and immune function (Mou et al., 2024). OsCPK4 also modulates OsRLCK176 degradation and accumulation in a phosphorylation state-dependent manner (Wang et al., 2018). Upon pathogen challenge or MAMP stimulation, OsCPK4 and OsRLCK176 mutually phosphorylate each other, forming a feedback loop that sustains OsRLCK176 stability through their kinase activities and phosphorylation events (Wang et al., 2018).

Chitin-triggered immunity is also finely regulated by E3 ubiquitin ligases to balance defense activation and cellular homeostasis. In rice, the E3 ligase SPL11 (spotted-leaf 11, also known as cell-death suppressor 2, SDS2), an S-domain receptor-like kinase, interacts with and phosphorylates SPL11, leading to reciprocal ubiquitination and degradation of SDS2 (Fan et al., 2018). SDS2 also interacts with OsRLCK118/176, which enhance immunity by phosphorylating the NADPH oxidase OsRbohB to stimulate ROS production (Fan et al., 2018). The U-box E3 ligase OsCIE1 acts as a molecular brake by ubiquitinating OsCERK1 during basal states, reducing its kinase activity. Upon chitin perception, activated OsCERK1 phosphorylates OsCIE1, inhibiting its ligase activity and releasing OsCERK1 from suppression (Wang et al., 2024). This dynamic interplay ensures that OsCERK1 is only active during pathogen challenge.

In A. thaliana, the OsCERK1 homolog AtCERK1/LYK1 plays a crucial role in chitin perception (Miya et al., 2007; Wan et al., 2008; Liu et al., 2012b). Chitin-induced homodimerization of AtCERK1/LYK1 is essential for its activation (Liu et al., 2012b). Downstream signaling events triggered by chitin, including MAPK activation and the ROS burst, are contingent upon the kinase activity of CERK1. By contrast, the Arabidopsis homolog of OsCEBiP, AtCEBiP/AtLYM2, exhibits high-affinity binding to CTOS but is not essential for AtCERK1-mediated chitin immune signaling (Shinya et al., 2012; Faulkner et al., 2013). Notably, lysin motif receptor kinase 5 (AtLYK5), which possesses inactive kinase domains, binds chitin with substantially higher affinity than AtCERK1 and interacts with AtCERK1 in a chitin-dependent manner (Figure 1B) (Cao et al., 2014). Chitin binding to AtLYK5 is essential for chitin-induced phosphorylation of AtCERK1 (Cao et al., 2014), suggesting that AtLYK5 serves as the primary chitin receptor, forming a chitin-inducible complex with AtCERK1 to initiate plant immunity. Phosphorylation of specific residues in the kinase domain of AtCERK1 (Y428, T479, S493, and T573) is essential for activating chitin-triggered defense responses (Suzuki et al., 2016, 2019). AtCPK5 directly phosphorylates AtLYK5 at S323/S542, modulating chitin-induced immunity (Huang et al., 2020). Interestingly, crosstalk between AtCERK1 and AtBAK1 is required for primed defense responses. AtBAK1 phosphorylates AtCERK1 at juxtamembrane residues (S268/S282/T283), enhancing chitin signaling efficiency without constitutive activation (Gong et al., 2019). This phosphorylation also regulates receptor endocytosis: chitin-induced AtCERK1 activity triggers the internalization of AtLYK5 (Erwig et al., 2017), dissociating the receptor complex after ligand perception. In addition, the E3 ligases PUB12/PUB13 negatively regulate chitin immunity by promoting the degradation of AtCERK1 and AtLYK5, highlighting the role of ubiquitination in terminating signaling (Liao et al., 2017; Yamaguchi et al., 2017).

Chitin signals are transduced via dynamic protein–protein interactions and phosphorylation events. A subgroup of RLCKs in the AtRLCK VII proteins, including AtPBL19, AtPBL27, and AtBIK1, specifically mediate chitin-triggered immune signaling and serve as crucial components of chitin-triggered MAPK activation (Rao et al., 2018). These kinases phosphorylate MAPKKK5 at S599 and MEKK1 at S603, thereby enhancing the activity of MAPKKK3/5 and MEKK1. This leads to the activation of two distinct MAPK cascades, MKK4/5–MPK3/6 and MKK1/2–MPK4, respectively. Activated MPK3/6 further phosphorylates MAPKKK5 at S682/S692, creating a positive feedback loop to amplify signaling, whereas activated MPK4 phosphorylates MEKK1, reinforcing cascade activation (Bi et al., 2018). Notably, the phosphorylation of MAPKKK5 by AtRLCK VII is enhanced when AtRLCK VII itself is phosphorylated by the chitin receptor AtCERK1 (Yamada et al., 2016; Bi et al., 2018), linking receptor activation to downstream cascade amplification.

Chitin-induced activation of AtRLCK VII extends to crosstalk with the ETI pathway. After chitin elicitation, AtPBL19 translocates from the PM to the nucleus via its N-terminal nuclear localization sequence (NLS). Meanwhile, in the cytoplasm, metacaspase-processed AtPBL19, which lacks an NLS, interacts with EDS1 and phosphorylates it, thereby promoting antifungal immunity. This dual subcellular role of AtPBL19 bridges PTI and ETI (Li et al., 2022). Chitin can also induce stomatal closure through a signaling module involving AtCERK1, AtRLCK VII, Ca²⁺, and S-type anion channel proteins such as SLAH3 and SLAC1 (Liu et al., 2019; Ye et al., 2020). AtPBL27 interacts with SLAH3 and phosphorylates it at S127 and S189, a step essential for chitin-induced stomatal closure (Liu et al., 2019). By contrast, CSOS do not induce stomatal closure but trigger Ca²⁺-dependent guard-cell death during fungal invasion (Figure 1B) (Ye et al., 2020). The mechanism by which CSOS are recognized remains unclear, although CSOS can directly permeabilize the M. oryzae cell membrane, thereby blocking appressorium-mediated infection (Lopez-Moya et al., 2021).

CERK1 and CERK1-like PRRs have been identified across diverse plant species, including monocots and dicots, and are recognized as central components of plant immunity (Yang et al., 2022). In tomato, the CERK1 ortholog Bti9 (also named SlLYK13) is required for chitin signaling and robust antibacterial immunity (Zeng et al., 2012). In wheat, TaCEBiP, TaLYK5, and TaCERK1 collectively mediate chitin responses (Liu et al., 2023b). In grapevine (Vitis vinifera), VvLYK1-1 and VvLYK1-2, orthologs of AtCERK1, participate in immunity triggered by CTOS, with VvLYK1-1 playing a vital role in basal resistance to Erysiphe necator (Brulé et al., 2019). VvLYK5-1 recognizes CTOS through its association with VvLYK1-1 (Roudaire et al., 2023). In apple (Malus domestica), MdCERK1-2 is involved in defense responses against A. alternata (Chen et al., 2020). In the liverwort species Marchantia paleacea, the receptor proteins MpaLYR and MpaCERK1 serve as PRRs that detect long-chain CTOS (CO₇/CO₈). Upon ligand binding, this receptor–ligand interaction initiates a cascade of signaling events, thereby enhancing the plant’s innate immunity against microbial pathogens (Tan et al., 2025).

Cellulose oligosaccharide perception and signaling

Cellooligomers induce Ca²⁺-dependent cell-wall integrity responses in Arabidopsis, with cellotriose being the most potent activator. These responses require the impaired in glycan perception (IGP1) protein, a receptor kinase that contains extracellular LRR and malectin domains (Tseng et al., 2022; Martín-Dacal et al., 2023). IGP1’s ECD binds CEL3 and CEL5 with high affinity, and it is indispensable for cellooligomer-induced cytoplasmic Ca²⁺ elevation, ROS bursts, MAPK activation, cellulose synthase phosphorylation, and regulation of cell-wall integrity genes (Tseng et al., 2022; Martín-Dacal et al., 2023). These findings establish IGP1 as a PRR for cellooligomers (Figure 2A). Co-receptors IGP2/IGP3 and IGP4 (encoded by AT1G56130 and AT1G56140), which also contain LRR-MAL domains, may function as components of the PRR complex for cellooligomer perception or as signaling partners in downstream PTI pathways (Fernández-Calvo et al., 2024). Notably, immunity triggered by fungal-derived cellooligomers often relies on CERK1 or acts synergistically with chitin (Johnson et al., 2018; Mélida et al., 2018), indicating that CERK1 may serve as a co-receptor or signaling hub in cellooligomer perception, particularly for MAMPs. This highlights the emerging role of LRR-MAL receptors in plant responses to cellulose-derived DAMPs and MAMPs, with potential for cross-reactivity among glycan receptors.

Figure 2.

Immune signaling pathway of plant-derived oligosaccharides.

(A) Cellooligosaccharides (CELs) can be recognized by AtIGP1. Upon this recognition, AtIGP1 (impaired in glycan perception) initiates a series of immune responses in Arabidopsis, including ROS bursts, Ca²⁺ influx, activation of MAPK activity, and upregulation of the defense-related gene WRKY. Homologs of AtIGP1, namely AtIGP2/3 and AtIGP4, also participate in the immune signaling process triggered by CELs. In addition, two malectin-LRR RKs, AtSIF2 and AtSIF4, play positive regulatory roles in CEL-triggered plant immunity. Moreover, hemicellulose-derived oligosaccharides such as XYLs, XA3XX, and MLGs activate the immune system in a manner that depends on AtIGPs and AtCERK1/AtLYK5. However, the identity of their specific recognition receptors remains to be clarified.

(B) The pattern recognition receptors for OG_10–15 are still unknown. Although wall-associated kinases (WAKs) can bind to OG_10–15, they do not contribute to the activation of immune signals. OG_10–15 can trigger a series of immune responses in soybean, including ROS bursts, activation of MAPK activity, and upregulation of the defense-related gene CYP93. Pectin oligosaccharides (POSs) are characterized by methylation and acetylation modifications, but it remains unclear which specific component of POSs plays the dominant role in immune activation. In soybean, GmCERK1 is involved in the immune response induced by POSs.

Beyond the IGP RKs, two malectin-LRR RKs, SIF2 (AT1G51850) and SIF4 (AT1G51820), are essential for cellooligomer-triggered immunity, likely acting as components of the PRR complex (Zarattini et al., 2021). This suggests that glycan perception involves multi-component receptor assemblies rather than single proteins. Characterizing the crosstalk among different types of RKs and downstream signaling components will clarify how plants integrate diverse PAMPs and DAMPs. Cellooligomers induce the upregulation of numerous defense-related genes, such as FLS2, SERK1, and MAPKKK (Tseng et al., 2022), indicating crosstalk between IGP RKs and other receptor kinases in PTI. Notably, synergistic interactions between PAMPs, such as flg22 or CTOS, and DAMPs, like cellooligomers, can amplify immune responses (Souza et al., 2017; Johnson et al., 2018). This priming effect enables plants to detect low-dose mixed elicitors, even when they are released at different time points, and mount robust defenses, highlighting the adaptability of plant immune systems. Interestingly, cellooligomers derived from pathogenic fungi activate immunity in Arabidopsis independently of BAK1 (Johnson et al., 2018). This suggests divergent mechanisms for glycan versus peptide PAMP signaling.

Plant berberine-bridge enzymes (BBEs) regulate cellooligomer homeostasis by oxidizing the anomeric carbon of CEL₃–CEL₆, thereby reducing their activity as DAMPs (Benedetti et al., 2018). This PTM represents a critical mechanism for the prevention of excessive immune activation during normal cellular processes. Further investigation into cellooligomer biosynthesis, degradation, and subcellular localization will deepen our understanding of how plants balance defense and development. In addition, AtPARN (AT1G55870), a poly(A)-specific ribonuclease, is essential for regulating cellooligomer-triggered immune responses. It is hypothesized that AtPARN modulates cellooligomer-induced Ca²⁺ elevation by shortening the poly(A) tails of specific mRNAs, thereby influencing mRNA stability and downstream signaling (Johnson et al., 2018). However, although its role in cellooligomer-mediated immunity has been characterized, the biological relevance of AtPARN in the context of natural pathogen infection or plant developmental processes remains to be determined. Clarifying the functional significance of this mRNA poly(A) tail-shortening mechanism is essential for deciphering whether AtPARN acts as a general regulator of immune signaling or serves specialized roles in specific biological contexts. This knowledge gap highlights the need for further investigation of how AtPARN-mediated mRNA stability control is integrated with plant defense against pathogens and developmental programs.

Hemicellulose oligosaccharide perception and signaling

IGP RKs are central to the activation of immune responses triggered by diverse glycans containing distinct carbohydrate moieties, such as Glc, Xyl, and Ara (Fernández-Calvo et al., 2024). These receptors not only function as primary sensors for cellooligomers but also participate in signaling induced by other hemicellulose oligosaccharides, including XYL4, XA₃XX, and MLG43 (Martín-Dacal et al., 2023; Fernández-Calvo et al., 2024). Despite structural and compositional variations, these glycans share a pyranose conformation and β-1,4-D-linkages, which may underlie their convergent recognition by IGP RKs through conserved molecular mechanisms. Although IGP1–4 contain LRR and MAL domains in their ECDs, their status as genuine PRRs for these hemicellulose oligosaccharides also requires validation through direct ligand-binding assays.

In A. thaliana, the recognition of MLG43, MLG443, β-1,3-glucan hexasaccharide (LAM6), and xylan oligosaccharides requires AtCERK1, although isothermal titration calorimetry (ITC) assays have shown that these ligands do not directly bind to the ECD of CERK1 (del Hierro et al., 2021; Fernández-Calvo et al., 2024; Mélida et al., 2018; Rebaque et al., 2021). This suggests that AtCERK1 functions as a co-receptor rather than a primary sensor. LYK4 and LYK5 make a partial contribution to the perception of MLG43 and xylan oligosaccharides, indicating a complex receptor network. In rice, MLG43/MLG443-triggered ROS bursts are abolished in Oscerk1 and Oscebip mutants (Yang et al., 2021). MLG43 and MLG443 bind to OsCERK1 and induce dimerization with the chitin receptor OsCEBiP to form an immune complex during M. oryzae infection (Yang et al., 2021). In addition, the lectin-RK OsLecRK1 is required for MLG perception in rice and binds MLGs in vitro (Dai et al., 2023), highlighting the presence of multi-component receptor systems for glycan sensing.

Pectin oligosaccharide perception and signaling

The molecular mechanisms underlying the perception of OG_10–15, key DAMPs derived from pectin degradation, are poorly understood. Early studies proposed WAKs as potential receptors for demethylesterified OG_10–15 on the basis of in vitro binding assays (Decreux and Messiaen, 2005; Decreux et al., 2006; Kohorn et al., 2009) and chimeric protein analyses (Brutus et al., 2010). However, genetic validation has been lacking. A recent study using a CRISPR-generated Arabidopsis mutant that lacked all five WAK genes demonstrated that WAKs are dispensable for OG_10–15-induced PTI, including the ROS burst and defense gene expression (Herold et al., 2025). These findings rule out WAKs as the primary receptors for OG_10–15.

In most cases, PAMP-induced plant disease resistance relies on the NADPH oxidase AtRBOHD, which generates ROS. ROS contribute to plant resistance through direct cytotoxic effects on pathogens, cell-wall strengthening, hypersensitive cell death, defense gene expression, and accumulation of antimicrobial compounds (Levine et al., 1994). However, in Arabidopsis, H_{2O2 production induced by} OG_10–15 does not enhance resistance to the necrotrophic fungal pathogen B. cinerea (Galletti et al., 2008). Instead, ROS-independent pathways, such as Ca²⁺ signaling, hormone accumulation, and expression of OG_10–15-responsive marker genes, play a critical role in defense against such pathogens (Moscatiello et al., 2006; Galletti et al., 2008). This highlights the context-dependent nature of immune mechanisms, in which necrotrophs may evade ROS-based defenses, necessitating alternative signaling pathways.

PL PsPL1 from P. sojae generates POSs with diverse methylation and acetylation patterns. In soybean, these POSs activate immunity in a GmCERK1-dependent manner (Figure 2B) (Sun et al., 2024), suggesting a role for LysM receptor kinases in the perception of pectin-derived DAMPs. The specific POS component(s) responsible for immune activation—whether a single oligosaccharide or a combination of modified structures—remains unclear. Mixed POSs could act synergistically, or a dominant oligomer (e.g., a specific DP or modification) could be the active ligand. Although WAKs are not required for OG_10–15 signaling, they and malectin-like receptor kinases (e.g., FERONIA/FER) have been linked to pectin oligosaccharide-induced adaptive responses such as cell-wall remodeling (Malivert et al., 2021; Moussu et al., 2023). However, direct binding of GalA-containing glycans to the ECDs of these receptors has not been demonstrated, leaving their roles as receptors or signaling partners unresolved.

The hyperaccumulation of OGs severely affects plant growth. A mechanism for controlling the homeostasis of OGs may rely on specific oligosaccharide oxidases encoded by the BBE gene family (Benedetti et al., 2018; Locci et al., 2019; Costantini et al., 2023; Salvati et al., 2025). For example, OG oxidases (OGOXs) oxidize and inactivate OGs to avoid deleterious, growth-affecting hyper-immunity and possible cell death. The inability of pathogens to use oxidized OGs as a carbon source also enhances plant disease resistance (Benedetti et al., 2018).

The interaction between rapid alkalinization factor (RALF) peptides and plant pectin drives the process of extracellular phase separation. This process induces the aggregation and promiscuous endocytosis of homologous and non-homologous receptors, thereby helping plants respond to complex environmental changes (Liu et al., 2024). In addition, plant growth requires cell-wall polysaccharides to be assembled into specific patterns. The interaction between RALF and its cell-wall-anchored proteins, leucine-rich repeat extensins (LRXs), is crucial for maintaining cell-wall integrity during responses to external stresses and pollen tube growth (Zhao et al., 2018; Moussu et al., 2020, 2023).

Counter-defense strategies of pathogens in response to oligosaccharide signaling

Pathogens have evolved sophisticated strategies to subvert oligosaccharide-activated immunity and successfully infect plants, and these can be categorized into distinct mechanistic frameworks for clarity.

Chitin deacetylation to evade receptor recognition

Fungal pathogens commonly secrete chitin de-N-acetylases (EC 3.5.1.41) into the apoplast, which remove acetyl groups from chitin to form chitosan (Figure 3A). This modification protects fungal hyphae from degradation by plant chitinases and inhibits the generation of immunogenic CTOS. For example, fully deacetylated CSOS cannot bind to CTOS receptors and thus fail to induce immune responses (Mauch et al., 1988; Baker et al., 2011; Xu et al., 2020). This strategy is conserved among fungal pathogens, as seen in studies showing that CSOS conversion disrupts receptor–ligand interactions (Petutschnig et al., 2010; Cord-Landwehr et al., 2016; Gubaeva et al., 2018; Gao et al., 2019).

Figure 3.

Strategies of pathogens for counter-defense to prevent oligosaccharide immunity.

(A) Pathogenic fungi secrete chitin deacetylase, which enzymatically hydrolyzes the acetyl groups of chitin oligosaccharides (CTOS). The resulting chitosan oligosaccharides (CSOS) cannot be recognized by LYK5 or CEBiP, thereby effectively inhibiting immune activation. This strategy enables the fungus to evade the host’s immune detection mechanism triggered by CTOS recognition.

(B) Pathogens secrete cell-wall-degrading enzymes to inhibit plant immunity. For example, the exo-polygalacturonase PehC can degrade OG_10–15. The short oligogalacturonides produced by this degradation process are incapable of activating plant immunity. Moreover, the chitinases secreted by pathogens break down CTOS into smaller fragments, rendering them unrecognizable by the corresponding receptors. Inactive chitinases, such as MoChia1 and MpChi, can compete with recognition receptors for CTOS binding, thus impeding immune activation. This competitive binding prevents the normal immune-triggering interaction between CTOS and the receptors, disrupting the plant’s immune response.

(C) Pathogens secrete effectors to inhibit plant immunity. Some effectors, like Mg1LysM and Avr4, protect chitin from degradation by plant chitinases. Mg1LysM, for example, can form a supramolecular structure through chitin-induced oligomerization of chitin-independent homodimers, which shields fungal chitin. In addition, pathogens can secrete proteins containing the LysM domain, such as Ecp6 and Slp1. These proteins competitively bind to CTOS, sequestering it and preventing its binding to the receptors. This competitive binding effectively blocks initiation of the immune response that would otherwise occur upon CTOS–receptor binding.

(D) Pathogens inhibit plant immunity through alternative pathways. For example, they secrete (GlcNβ1,4GlcNAc)₄, which inhibits formation of the CTOS–OsCEBiP–OsCERK1 “sandwich” structure. This disruption prevents normal formation of the signal transduction complex, thereby blocking the immune activation cascade. Pathogens also secrete the effector Xoo1488 into the cytoplasm, thus inhibiting the phosphorylation of OsRLCK185 by OsCERK1. This inhibition of phosphorylation disrupts downstream signaling events, particularly activation of the MAPK pathway. Pathogens can also secrete the E3 ubiquitin ligase AvrPtoB, which targets CERK1 for degradation. This CERK1 degradation effectively suppresses CTOS signal transduction, as CERK1 is a crucial component in the immune-signaling cascade.

(E) Pathogens suppress plant immunity by oxidizing immunocompetent oligosaccharides. Pathogens secrete the auxiliary activity family 7 (AA7) protein to oxidize specific OG_10–15. The oxidatively modified OG_10–15 cannot be recognized to activate plant immunity. However, oxidized OG_10–15 can be degraded by pathogen-secreted pectinases, and the generated galacturonic acid (GalA) can serve as a carbon source to facilitate pathogen growth.

Degradation of immunogenic oligosaccharides by cell-wall enzymes

Pathogenic fungi deploy CWDEs to disrupt oligosaccharide-mediated signaling (Figure 3B). Ralstonia solanacearum secretes the exo-PG PehC, which hydrolyzes immunogenic OG_10–15 into non-immunogenic GalA, dampening PTI. Notably, R. solanacearum uses GalA as a carbon source, linking immune suppression to nutrient acquisition (Ke et al., 2023). Fungal effectors, like the chitinase-active effectors (EWCAs) of Podosphaera xanthii, degrade CTOS at infection sites, whereas inactive chitinases from M. oryzae (MoChia1) and Moniliophthora perniciosa (MpChi) act as chitin chelators, sequestering CTOS from plant receptors (Fiorin et al., 2018; Yang et al., 2019; Martínez-Cruz et al., 2021).

Chitin-binding proteins as physical barriers

Fungi use chitin-binding proteins to shield CTOS from plant detection, either by blocking chitinase degradation or receptor binding (Figure 3C). The fungal effector Mg1LysM forms supramolecular structures to protect cell walls from host chitinases (Sánchez-Vallet et al., 2020). Secreted LysM protein 1 (Slp1) from M. oryzae competes with the rice chitin receptor OsCEBiP for CTOS binding, thus preventing formation of the OsCEBiP–OsCERK1 immune complex and downstream signaling (Mentlak et al., 2012). Extracellular protein 6 (Ecp6) and Avr4 secreted by Cladosporium fulvum sequester CTOS or bind chitin directly, respectively, to evade recognition (van den Burg et al., 2006, de Jonge et al., 2010). These effectors, which often contain LysM domains, act as physical barriers to ligand–receptor interactions (Marshall et al., 2011; Takahara et al., 2016; Kombrink et al., 2017).

Interference with receptor signaling cascades

Pathogens disrupt CTOS signaling at the receptor or downstream kinase level (Figure 3D). A synthetic oligosaccharide (GlcNβ1,4GlcNAc)₄ inhibits CEBiP dimerization by disrupting ligand–receptor interactions (Hayafune et al., 2014). Bacterial effectors like AvrPtoB target CERK1 for ubiquitination and degradation, whereas Xoo1488 from X. oryzae suppresses OsCERK1-mediated phosphorylation of OsRLCK185, halting MAPK activation (Gimenez-Ibanez et al., 2009; Yamaguchi et al., 2013). These strategies directly abrogate the early signaling steps required for immune activation.

Oxidation of DAMPs to suppress immunity

Pathogens can secrete FAD-binding BBE-like enzymes to oxidize immunocompetent oligosaccharides, thereby interfering with oligosaccharide signaling. For example, the auxiliary activity family 7 (AA7) protein selectively oxidizes OG_10–15, impairing their recognition by plant immune receptors (Turella et al., 2025). Notably, AA7-mediated oxidation, when combined with OG-degrading enzymes, promotes the accumulation of GalA monomers that serve as nutrients for pathogen growth (Momeni et al., 2021; Turella et al., 2025). This dual strategy enables pathogens to suppress plant immune responses while facilitating their colonization.

Each strategy highlights how pathogens have evolved multifaceted mechanisms to subvert plant immunity, with plants, in turn, developing counter-defenses like ligand rescue (e.g., rice OsTPR1 blocking MoChia1) (Yang et al., 2019) to maintain defense efficacy.

Concluding remarks and perspectives

Oligosaccharide complexity and immune signaling challenges

Plant and microbial oligosaccharides exhibit extraordinary structural diversity, posing challenges for the isolation of elicitors and the dissection of signaling pathways. In model plants like rice and Arabidopsis, CTOS-triggered immunity relies on distinct receptors (OsCEBiP/AtLYK5) but converges on the co-receptor CERK1 for signal transduction (Kaku et al., 2006; Liu et al., 2012b; Cao et al., 2014; Hayafune et al., 2014). This conserved architecture warrants investigation in non-model species (e.g., legumes) to understand pathogen recognition across plant lineages.

Role of chitin deacetylation in immune evasion and agriculture

CSOS show weak binding to CERK1, but their high solubility and low toxicity make them valuable immune inducers in agriculture (Iriti and Faoro, 2009). Revealing the molecular mechanisms that underlie CSOS-triggered plant immunity could enhance crop disease resistance. Although the specific receptors for CSOS recognition in plants remain to be identified, the discovery that macrophages from blunt snout bream (Megalobrama amblycephala) recognize CSOS through the mannose receptor C-type lectin-like domain 4–8 (MaMR CTLD_4–8) provides valuable insight for potential plant receptor identification (Ouyang et al., 2021). The degree of chitosan acetylation, which is a key determinant of its physicochemical properties, remains an unaddressed factor in immune recognition (Iriti and Faoro, 2009).

Structural gaps in oligosaccharide–receptor interactions

The crystal structure of the CERK1–CTOS complex has clarified chitin recognition, but receptor structures for other oligosaccharides (e.g., IGP RKs) remain unknown. Conserved phenylalanine residues in Arabidopsis MAL domains are hypothesized to mediate CEL3 perception, but direct ligand-binding assays (e.g., ITC and SPR) are needed for validation. Characterizing these complexes will reveal conserved glycan-recognition principles and inform the design of synthetic elicitors.

Unidentified receptors for immunogenic oligosaccharides

Many oligosaccharide activators lack characterized receptors; these include OG_10–15, a key DAMP in plant defense. Pectin oligosaccharides derived from pathogen-secreted enzymes vary in polymerization and modification, but whether high-DP fragments or specific modifications (e.g., acetylation) drive immunogenicity is unclear. AOSs and MLGs also require receptor identification to decode their signaling mechanisms.

Technological frontiers in oligosaccharide research

Advanced techniques like MS-based glycomics will enable in vivo profiling of pathogen-induced cell-wall modifications and purification of bioactive DAMPs (Ropitaux et al., 2022; Sun et al., 2024). Gene editing and marker-assisted breeding can leverage identified receptors to enhance defense pathways (Voxeur et al., 2019; Ropitaux et al., 2022; Sun et al., 2024). Nanotechnology can further extend oligosaccharide potential: chitin nanofibers induce stronger immune responses than CTOS in soybean, and nanocomplexes (e.g., cellobiose–SPc) synergize to upregulate defense genes (Kaminaka et al., 2020; Wang et al., 2023b). These approaches connect fundamental glycan biology to sustainable agriculture, offering eco-friendly alternatives to chemical pesticides.

Funding

This work was supported by the National Key Research and Development Program of China (grant nos. 2022YFF1001500 and 2023YFE0123400), the China Postdoctoral Science Foundation (grant no. 2024T170421, G.S.), the Jiangsu Funding Program for Excellent Postdoctoral Talent (grant no. 2023ZB236, G.S.), the Postdoctoral Fellowship Program of CPSF (grant no. GZC20231129, G.S.), and the Key Research and Development Program of Guangdong Province (grant no. 2022B0202080004).

Acknowledgments

No conflict of interest declared.

Author contributions

G.S., Y.X., and Y.M.W. wrote and edited the article. H.Y., K.Y., and Y.C.W. reviewed and edited the article. G.S. designed the figures and prepared Supplemental Table 1.

Published: August 5, 2025