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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 2023 Aug 25;214(2):144–153. doi: 10.1093/cei/uxad102

MAIT cells in bacterial infectious diseases: heroes, villains, or both?

Sihong Wu 1, Xi Yang 2, Yongliang Lou 3,, Xingxing Xiao 4,
PMCID: PMC10714195  PMID: 37624404

Abstract

Due to the aggravation of bacterial drug resistance and the lag in the development of new antibiotics, it is crucial to develop novel therapeutic regimens for bacterial infectious diseases. Currently, immunotherapy is a promising regimen for the treatment of infectious diseases. Mucosal-associated invariant T (MAIT) cells, a subpopulation of innate-like T cells, are abundant in humans and can mount a rapid immune response to pathogens, thus becoming a potential target of immunotherapy for infectious diseases. At the site of infection, activated MAIT cells perform complex biological functions by secreting a variety of cytokines and cytotoxic substances. Many studies have shown that MAIT cells have immunoprotective effects because they can bridge innate and adaptive immune responses, leading to bacterial clearance, tissue repair, and homeostasis maintenance. MAIT cells also participate in cytokine storm generation, tissue fibrosis, and cancer progression, indicating that they play a role in immunopathology. In this article, we review recent studies of MAIT cells, discuss their dual roles in bacterial infectious diseases and provide some promising MAIT cell-targeting strategies for the treatment of bacterial infectious diseases.

Keywords: bacterial infectious disease, immunopathology, immunoprotection, immunotherapy, MAIT cells


MAIT cells can be activated in a TCR-dependent manner and/or cytokine-dependent manner. Upon activation, MAIT cells may play a protective role or pathological role in bacterial infections. Therefore, clarifying the functions of MAIT cells in bacterial diseases is a crucial step for the application of MAIT cell-targeting immunotherapies in the clinic.

Introduction

In recent years, the incidence of bacterial infectious diseases has shown an upward trend because of climate change and the aging population, making it a major public health emergency [1, 2]. Cases of multidrug-resistant bacterial infections are on the rise and becoming particularly serious and life threatening [3, 4]. Antibiotics are the first choice for the treatment of bacterial diseases; however, the emergence and spread of drug-resistant bacteria have made the treatment regimen limited in hospitalized patients due to the abuse of antibiotics [5, 6]. In addition to the administration of antibiotics, immunotherapy is another promising regimen for the treatment of bacterial diseases [7, 8]. The innate immune system is the first line of defense against pathogenic invasion, and it has the characteristic of a fast response and plays an important role in the inflammatory response to pathogenic infection [9, 10]. The second line of defense against pathogenic infection is the adaptive immune system, which can launch highly specific and strong immune responses [11, 12]. Because these two immune systems have vital roles in anti-infection [13, 14], tissue repair [15, 16], and the maintenance of homeostasis [17, 18], many researchers have been exploring their applications in many fields through targeting immune cells [19], immune molecules [20], or pathogenic bacteria [21], such as immunotherapy [22], infectious disease prevention and control [23] and disease diagnosis [24].

Innate-like T cells, a type of immune cells that acts as a bridge in the immune system, not only have the characteristics of innate immune cells but can also initiate an adaptive immune response and accelerate the immune response against invaders [25–27]. Mucosal-associated invariant T (MAIT) cells, a subpopulation of innate-like T cells discovered in 1993 [28], were named by Treiner et al.[29], and since then, the biological characteristics of MAIT cells and their roles in bacterial infectious diseases have been regularly revealed by many studies [30–33]. MAIT cells display a semi-invariant T-cell receptor (TCR) and can be activated by riboflavin-related derivatives presented by the highly conserved major histocompatibility complex class I-related molecule, MR1, in mammals [29, 34–37], implying that MAIT cells play an important role in the immune system. Moreover, MAIT cells can also be activated by cytokines, such as IL-2, IL-12, and IL-18 (Fig. 1) [38, 39].

Figure 1.

Figure 1.

Mucosal-associated invariant T (MAIT) cells in bacterial infectious diseases. In bacterial infectious diseases, pathogens or riboflavin metabolisms are captured by antigen-presenting cells (APCs), which can activate MAIT cells in a TCR-dependent manner or cytokine (CK)-dependent manner. Upon activation, MAIT cells proliferate, secrete abundant cytokines, and then recruit and activate other immune cells, acting as a bridge to link innate and adaptive immunity. Activated MAIT cells act as heroes, villains, or both in different bacterial infectious diseases.

Upon activation, MAIT cells can initiate a rapid immune response [40, 41], produce a series of cytokines and cytotoxic substances to kill pathogens [42–47], repair impaired tissue and maintain homeostasis [48–51], launch adaptive immunity [52, 53], and trigger other immune cells to participate in immune defense (Fig. 1) [54]. Meanwhile, activated MAIT cells can also cause some adverse consequences, such as cytokine storm [55, 56], tissue fibrosis [57, 58], and the initiation and metastasis of tumor cells [59, 60]. In this review, we briefly summarize the biological characteristics of MAIT cells, focus on the roles of MAIT cells in bacterial infectious diseases, and finally discuss the therapeutic strategies targeting MAIT cells in bacterial infectious diseases and some pending questions that need to be addressed.

Biological properties of MAIT cells

Phenotype and tools

MAIT cells are abundant in the peripheral blood (1–10%) and liver (15–50%) of humans [61–63], and express an invariant TCRα chain (human: Vα7.2-Jα33; mouse: Vα19-Jα33) paired with a limited number of TCRβ chains (Vβ2, 13, and 22 in humans and Vβ6 and 8 in mice) [28, 29, 36] and many different markers or receptors correlated with the biology of MAIT cells. For example, IL-12R, IL-15R, IL-18R, and IL-23R, the cytokine receptors expressed on MAIT cells, are correlated with the cytokine-dependent activation of MAIT cells [38, 39, 64–66]; CXCR6, CCR2, CCR5, and CCR6, the tissue chemokine receptors, make that MAIT cells migrate to infected tissues [64, 67].

For our understanding of MAIT cells, the tools used to identify MAIT cells have been enriched several times, from specific TCRα primers [36] to specific antibodies (anti-Vα7.2 and anti-CD161) [68] to MR1-Ag (MR1-rRL-6-CH2OH and MR1-5-OP-RU) tetramers [69, 70]. Every new generation of tools can improve or even overcome the limitations that the last one has in identifying MAIT cells, which realizes the more accurate identification of MAIT cells. Therefore, the MR1-Ag tetramer is currently the optimized tool for identifying human and mouse MAIT cells [71, 72]. To overcome the issue that the frequency of MAIT cells is extremely low in laboratory mouse strains [73], researchers also constructed a transgenic mouse, the B6-MAITCAST mouse, in which MAIT cells are abundant, as an animal model to study MAIT cells [74]. However, this mouse strain is not widely used because of problems with transportation and customs clearance. Currently, one feasible solution to this issue is to proliferate MAIT cells by vaccinating mice before the experiment. Usually, researchers use bacteria with a riboflavin metabolic pathway and their lysates [45, 46] or 5-OP-RU with TLR agonist ligands [75] as vaccines.

Heterogeneity

MAIT cells have two main characteristics: expression of a semi-invariant TCR and restriction by the highly conserved MR1 molecule [76], implying the homogeneity of MAIT cells. However, recent studies have indicated that MAIT cells are functionally heterogeneous [77, 78]. The secretion of cytokines and cytotoxic substances is related to the distribution of MAIT cells [72, 79]. MAIT cells secrete IL-17 in the liver [80], oral [81], and female reproductive tract [82] after activation, while MAIT cells mainly secrete IFN-γ and TNF in the peripheral blood [47] and intestinal mucosa [83]. Moreover, when stimulated by Escherichia coli, MAIT cells secrete more cytokines (IFN-γ and IL-22) in the fetal small intestine than circulating MAIT cells [84], which may protect the newborn from bacterial infection. In addition, the function of MAIT cells is also related to the context. Although MAIT cells are abundant in mucosal tissues, they are not activated in healthy conditions, but are only activated after pathogenic infections [85–87]. Therefore, the activation of MAIT cells is related to the inflammatory factor environment [75, 86, 88, 89], indicating that MAIT cell function is context dependent. Furthermore, the activation way of MAIT cells is related to the time of stimulation [90]. In an in vitro experiment, Klenerman’s team found that when CD8+ T cells were cocultured with E. coli infected THP-1 cells, MAIT cells had different activation ways at different times: early activation was MR1 dependent after 5 hours of coincubation, and late activation was dependent on MR1 and IL-12 and IL-18 after 20 hours of coincubation [90]. In addition, distinct results may be obtained from the different species of animal models used to study MAIT cell function [91, 92]. Even if the species are the same, the way they are modeled could also affect the results [93, 94].

Antigens

Initially, researchers found that some bacteria could activate MAIT cells [47, 95]. Furthermore, the lysates [96, 97] and metabolites [70, 76, 98] of some bacteria can also activate MAIT cells. Moreover, some drugs and drug-like molecules also act as agonists or inhibitors of MAIT cell activation [99]. Among the metabolites of the bacteria, 5-OP-RU and 5-OE-RU [70], the derivatives of vitamin B2 (VB2), are currently known to be the two strongest agonists in activating MAIT cells. 6-FP, a photodegradation product of VB9, was the first described ligand of MR1 and plays an inhibitory role in activating MAIT cells [76]. Among drugs, diclofenac and its metabolites, methotrexate and aminopterin can activate MAIT cells [99]. Among drug-like molecules, 3-F-SA has a comparable ability to 6-FP in inhibiting the activation of MAIT cells [99]. Therefore, these drugs or drug-like molecules may also modulate the function of MAIT cells in addition to exerting their own effects when they are administered to patients.

Activation

The first described activation manner of MAIT cells is MR1-dependent manner through the MR1-TCR axis in bacterial infectious diseases [47, 76, 95]. In addition, MAIT cells can also be activated in a cytokine-dependent manner through IL-18 with IL-12, IL-15, and/or interferon α/β (Fig. 1) [38, 39, 100], which is mainly present in viral diseases [39], autoimmune diseases [58], and the diseases caused by bacteria without a riboflavin biosynthesis pathway [55]. Unsurprisingly, these two activation manners of MAIT cells are not mutually exclusive in diseases caused by some bacteria, such as Mycobacterium bovis [44] and E. coli [101], which can activate MAIT cells in a TCR- and cytokine-dependent manner. Through intranasal inoculation with riboflavin-deficient Salmonella typhimurium and/or 5-OP-OU, Chen et al. found that only inoculation with both could trigger the activation and accumulation of MAIT cells [75], indicating that the activation and accumulation of MAIT cells in vivo require the participation of both antigens and cytokines. Moreover, compared to the single manner of activation, the dual-dependent mechanism can achieve a stronger and more sustained activation of MAIT cells and enhance their cytotoxic effect [100]. Apart from antigens and/or cytokines, the activation of MAIT cells also requires secondary signals. Consistent with conventional T cells, ICOS/ICOS-L signaling is also involved in the activation and RORγt expression of MAIT cells [102]. In addition, OX40/OX40L signaling can promote the activation and proliferation of MAIT cells and then the production of IL-9—which is correlated with the severity of Helicobacter pylori-induced gastritis—by activated MAIT cells during H. pylori infection [103]. Upon activation, MAIT cells upregulate the expression of CD25 and CD69, secrete type 1 cytokines (IFN-γ and TNF-α) and/or type 17 cytokines (IL-17 and IL-22), and produce GzmB and perforin [31, 43, 45, 61, 104, 105]. These cytokines can protect the host against infection [45, 47] but can also aggravate some diseases [89, 106].

Roles of MAIT cells in bacterial infectious diseases

Protection

The first confirmed role of MAIT cells was their antibacterial function reported in 2010 [47, 95]. Subsequently, a growing number of studies suggest that mouse and human MAIT cells can play a protective role in infectious diseases caused by bacteria, such as Streptococcus pneumoniae [107], Klebsiella pneumoniae [108], Francisella tularensis [46, 109], and Legionella longbeachae [45]. In bacterial infectious diseases, MAIT cells perform antibacterial functions not only by secreting cytotoxic substances but also by recruiting and activating other immune cells [42, 54, 110, 111]. Furthermore, MAIT cells have a positive significance in the treatment of drug-resistant bacteria through secreting GzmB, perforin, and granulysin in an in vitro experiment conducted using human PBMCs [33, 112]. Moreover, an ex vivo study showed that human MAIT cells can act as an effector arm of humoral immunity against bacteria via IgG-mediated opsonization, which markedly enhances the capacity of APCs to phagocytize the target pathogen and present antigen via MR1, ultimately prompting MAIT cells to mount a strong and fast response against pathogenic infection in patients [113].

Apart from anti-bacterial properties, MAIT cells may also play a role in controlling tissue repair and homeostasis (Fig. 1) [48–51, 114, 115]. Salou et al. first proposed the hypothesis that MAIT cells are implicated in tissue repair [32], which was then proven by Constantinides et al. [51], Lamichhane et al. [50], Leng et al. [48], and Hinks et al. [49]. MAIT cells can express multiple genes that are related to tissue repair and wound healing [48–51] and possess a similar transcriptional profile as γδ T cells [116, 117] and H2-M3-restricted CD8+ T cells [49, 118], implying the tissue repair function of MAIT cells. Indeed, Leng et al. found that culture supernatants obtained from E. coli-stimulated human CD8+ MAIT cells could significantly promote the wound closure of the monolayer of colonic Caco2 cells, and this phenomenon was inhibited by an anti-MR1-blocking antibody [48]. Moreover, using experimental mouse models, Constantinides et al. found that the epidermal tongue length of the MAIT-sufficient Tcrd−/− mice topically associated with Staphylococcus epidermidis or the WT mice topically administered with 5-OP-RU was significantly longer than those observed in the MAIT-deficient Mr1−/−Tcrd−/− mice with no S. epidermidis applied or the mice with no 5-OP-RU treatment, respectively [51].

Because of their anti-infectious properties, MAIT cells can also be used as the target of vaccines or vaccine adjuvants to enhance MAIT cell-mediated protection against subsequent infections [26, 45, 102, 109, 119, 120]. MAIT cells that are enriched in the mucosa with a capacity against bacterial infections [29, 32, 104] can participate in adaptive immune responses [26, 120–122], form a stable memory-like MAIT-1 cell population in a mouse model infected with F. tularensis [109] and be boosted when mice are vaccinated with 5-OP-RU in association with different TLR agonists [75]. These properties imply that a MAIT cell-targeting vaccine can be used to boost host resistance by augmenting MAIT cell-mediated immunity. Indeed, multiple studies have proven the potential effects of MAIT cell-targeting vaccines in defending against bacterial infections. The first inspiring study investigating the role of 5-OP-RU as a “vaccine” was reported by Wang et al. [45]. They found that the mice boosted by 5-OP-RU in combination with the TLR agonist CpG or Pam2Lys had more lung MAIT cells than the naïve mice, and upon L. longbeachae challenge, the bacterial burden was significantly lower in the boosted WT mice than in the boosted MR1−/− mice, suggesting that 5-OP-RU inoculation promotes MAIT cell proliferation and then enhances host defense against bacterial infections. Furthermore, consistent with 5-OP-RU plus a TLR agonist, Wang et al. found that in a vaccinated mouse model 5-OP-RU plus IL-23 could also enhance host immunity to clear L. longbeachae [102]. Moreover, 5-OP-RU may also be used as a mucosal adjuvant to enhance bacterial vaccine efficacy through MAIT cell-mediated B-cell help [26, 120, 121]. Jensen et al. investigated the ability of 5-OP-RU as the adjuvant of a Vibrio cholerae O1 polysaccharide conjugate vaccine in a mouse model and found that mice could produce a higher level of mucosal IgG antibodies in the 5-A-RU plus methylglyoxal group than in the methylglyoxal alone group, protecting vaccinated mice from subsequent V. cholera challenge [120].

MAIT cells, as an innate-like T-cell subpopulation, can bridge innate and adaptive immunity. After activation by bacteria, MAIT cells secrete multiple cytokines to crosstalk with monocytes, dendritic cells (DCs), B cells, and neutrophils and then mount and/or fine tune immune responses [26, 54, 123, 124]. Mouse MAIT cells activated by F. tularensis LVS can promote the early production of pulmonary GM-CSF, which is necessary for the differentiation of inflammatory monocytes into monocyte-derived DCs (Mo-DCs), and Mo-DCs trigger the activation and accumulation of CD4+ T cells in the lungs [54]. In addition, human MAIT cells activated by the cognate Ag 5-A-RU/MG can upregulate the expression of CD40L and induce CD40L- and MR1-dependent DC maturation, and DCs then upregulate IL-12 expression, which in turn promotes MAIT cell activation and provides help to efficiently prime CTLs [123]. Microbe-activated human MAIT cells can promote plasmablast formation and antibody production by secreting B-cell stimulatory factors in in vitro experiments [121]. Furthermore, Jensen et al. reported that the adaptive transfer of CXCR5+ T follicular helper-like MAIT cells into αβ T-cell deficient mice enhances host humoral immune responses to V. cholerae by expressing B-cell helper cytokines (IL-21, IL-10, and BAFF), indicating a protective role of mouse MAIT cells against V. cholerae infection [26]. Moreover, the mutual restriction between MAIT cells and neutrophils may be present in humans to balance immune responses [124]. Although activated MAIT cells can recruit neutrophils to augment immune responses [50], strongly activated MAIT cells induce neutrophil death by producing a high level of TNF-α; in turn, neutrophils inhibit the overactivation of MAIT cells in a cell-contact and ROS-dependent manner [124], suggesting a negative regulatory feedback mechanism to protect the host from excessive inflammation and respond to bacterial infection.

Pathology

Although many studies have reported the protective function of MAIT cells against bacterial infections, their pathogenic role exists in some settings (Supplementary Table S1). Upon activation by superantigens (SAgs), human MAIT cells launch a robust proinflammatory cytokine response by producing large amounts of IFN-γ and TNF-α, which may lead to a systemic cytokine storm and could be life-threatening for the host [55, 56]. Moreover, in a H. pylori infection model, D’souza et al. found that 5-OP-RU-treated mice displayed more serious gastric pathology than mice without MAIT cell expansion, suggesting that MAIT cells may be implicated in the pathological process of gastritis caused by H. pylori [89]. This mechanism may be related to MAIT cell-secreted IFN-γ, TNF-α, and IL-17A [89, 125].

Recently, several reports demonstrated that MAIT cells are involved in tissue repair and homeostasis when activated by commensal bacteria or pathogenic bacteria, which is a novel role of MAIT cells in maintaining host health [48–51]. However, it has also been reported that MAIT cells executing an improper tissue repair function may lead to tissue fibrosis in the liver [57, 58] and kidney [126] and may also promote tumor growth by expressing tissue repair- and/or angiogenesis-related genes [41, 114]. In patients with alcoholic liver diseases, if intestinal barrier integrity is damaged, liver MAIT cells can be activated by bacteria from the gut and then secrete cytokines and cytotoxic substances [127, 128], aggravating liver inflammation and fibrosis [129, 130]. In addition, MR1 can be expressed in many cells [131], which means that they can activate MAIT cells using agonist ligands. Although MAIT cell antigens in cancer have not yet been identified, the existence of bacteria inside or on the surface of the tumor has been verified [132]; therefore, bacterial antigens presented by tumor cells can activate and recruit MAIT cells, which has been proven to have protumor effects [59, 133].

Researchers also found that MAIT cells could suppress host immune responses by communicating with other immune cells in certain bacterial infectious diseases [42, 54, 110, 111]. Sakai et al. found that in an experimental mouse model, the activated MAIT cells of mice vaccinated with 5-OP-RU + CpG inhibited CCR2+Ly6C+ myeloid cells trafficking into the mLNs in a TGF-β-dependent manner, which delayed the priming of Mycobacterium tuberculosis-specific CD4+ T cells and affected the adaptive immune response [93]. Moreover, in the S. typhimurium BRD509 or Pam2Cys plus 5-OP-RU preprimed mouse model, activated MAIT cells recruited immune cells, including neutrophils, macrophages, eosinophils, and dendritic cells, into the H. pylori-infected gastric mucosa, which aggravated gastritis [89, 134]. In addition, in some tissues, MAIT cells can recruit neutrophils into the infected site through the secretion of IL-17 [135, 136]. These recruited neutrophils may exacerbate tissue inflammation by secreting a panel of cytokines and cytotoxic substances [137, 138]. Importantly, in research on tumor immunology, MAIT cells can suppress the anti-tumor function of NK cells and enhance the permeability of the tissue mucosal and/or vascular barrier [59, 139], which results in the translocation of flora [140], aggravates the inflammatory response, and promotes tumor metastasis.

MAIT cell-targeting strategies for antibacterial therapy

As a subpopulation of innate-like T cells, MAIT cells can launch a rapid, non-specific innate immune response and mount a specific adaptive immune response upon activation, endowing them with a versatile function in antibacterial infectious diseases [25, 54]. Noteworthily, the function(s) of MAIT cells in bacterial diseases must be taken into consideration when MAIT cell-targeting strategies are used to treat these diseases [45, 61, 89].

Given the excellent protective role of MAIT cells in bacterial infectious diseases, MAIT cells can be considered a therapeutic target through priming and expanding them by using agonist ligands or vaccine strains [93, 120, 141, 142]. First, MAIT cells display a good protective effect against infections by intractable bacteria, such as superbacteria [112]. Second, MAIT cells can also be used as the target of vaccine adjuvants to enhance bacterial vaccine efficacy [26, 45, 120]. Third, based on the immune checkpoints expressed on the surface of MAIT cells [111, 143, 144], MAIT cells can also act as targets to treat infectious diseases [145, 146]. PD-1, a well-known immune checkpoint [147], is also expressed on MAIT cells [88, 144, 145]. In patients with active tuberculosis, the expression of PD-1 on MAIT cells in pleural effusion was high and correlated with the deficiency of IFN-γ [144], and the secretion of IFN-γ was restored to exert anti-bacterial effects by using purified PD-1 antibody, implying that PD-1 might be a new therapeutic target of bacterial infectious diseases [144].

Given that MAIT cells also play a pathological role in some diseases, inhibiting MAIT cell activation or neutralizing the cytokines and cytotoxic substances secreted by MAIT cells may also be a new therapeutic strategy. Superantigens that are expressed by some bacteria can activate MAIT cells and cause a cytokine storm [55, 56]. The inhibitor ligands of MAIT cells, such as 6-FP [148] and Ac-6-FP [149], can be taken into consideration in the treatment of diseases. This strategy has been studied in the treatment of tumors [59], inflammatory bowel disease [150], and so on. In addition, Barber’s team found that the activation of MAIT cells delayed the priming of Mtb-specific CD4+ T cells, which indicates that using an inhibitor ligand may be a candidate strategy for tuberculosis treatment [93]. Furthermore, in patients infected with H. pylori [89], IL-17A neutralizing antibody may be a good choice to alleviate the pathological responses caused by MAIT cells, such as gastric mucosal injury and gastritis.

Concluding remarks

Since MAIT cells were first discovered in 1993, they have become a star player in the field of T-cell immunity due to their nonredundant functions in the immune system. In the past several decades, the enigmatic veils of MAIT cells in phenotype, antigen, activation, and development have been revealed. MAIT cells are a double-edged sword, unfortunately, and how to avoid their pathogenicity when using the protective role of MAIT cells is the most important aspect of MAIT cell research.

Although the role of MAIT cells in some diseases has been clarified, further studies are needed to comprehensively elucidate the functions of MAIT cells in bacterial infectious diseases. First, based on their location, MAIT cells are divided into two categories, peripheral blood-circulatory MAIT cells and tissue-resident MAIT cells. However, the relationship between these two groups and whether the conclusions can be extended to each other are not clear. It has been reported that the number and molecular phenotype of MAIT cells in peripheral blood are different from those of tissue-resident MAIT cells, and their responses to pathogenic bacteria are also different [72, 79]; therefore, further studies are needed to investigate these two groups of MAIT cells. Second, although there is abundant commensal flora in the gastrointestinal tract, some of these bacteria have a riboflavin metabolic pathway that can produce riboflavin metabolic derivatives that activate MAIT cells. In an in vivo environment, MAIT cells are not continuously activated to produce excessive cytokines, but only when they are infected by pathogenic bacteria are MAIT cells activated to exert antibacterial effects [87]. However, the definite mechanism of this condition is still unclear. Third, the current studies on the antibacterial function of human MAIT cells have mainly focused on PBMC-derived MAIT cells. The role and mechanism of MAIT cells in response to bacterial infectious diseases in humans are still not clear, which is not conducive to the clinical application of MAIT cells. Based on the existing conclusions, we found that the number of MAIT cells in the infection site is often increased and that the increased MAIT cells can secrete antibacterial cytokines; therefore, MAIT cells can be used as a new target for antibacterial therapy [42, 45, 93, 108].

For bacterial infectious diseases, treatment is still a major challenge due to the abuse of antibiotics, climate change, and rising population mobility. In addition to the development of new antibiotics, immunotherapy is another promising candidate for the treatment of bacterial diseases. Many studies have suggested that MAIT cells can play important roles in bacterial infectious diseases. However, MAIT cells not only act as heroes but also as villains in some diseases. Therefore, clarifying the functions of MAIT cells in the progression of diseases and formulating a personalized therapeutic scheme is a crucial step for the application of MAIT cell-targeting immunotherapies in the clinic.

Supplementary Material

uxad102_suppl_Supplementary_Table_S1

Glossary

Abbreviations

3-F-SA

3-formylsalicylic acid

5-A-RU

5-amino-6-D-ribitylaminouracil

5-OE-RU

5-(2-oxoethylideneamino)-6-D-ribitylaminouracil

5-OP-RU

5-(2-oxopropylideneamino)-6-D-ribitylaminouracil

6-FP

6-formylpterin

Ac-6-FP

acetyl-6-formylpterin

APC

antigen-presenting cell

BAFF

B-cell activating factor

CTL

cytotoxic T cells

DC

dendritic cell

GM-CSF

granulocyte-macrophage colony-stimulating factor

ICOS

inducible costimulator

IFN

interferon

MR1

major histocompatibility complex class I-related protein 1

MAIT

mucosal-associated invariant T

PBMC

peripheral blood mononuclear cell

ROS

reactive oxygen species

rRL-6-CH2OH

reduced 6-hydroxymethyl-8-D-ribityllumazine

TCR

T-cell receptor

THP-1

Tohoku Hospital Pediatrics-1

TLR

Toll-like receptor

TNF

tumor necrosis factor

TGF

transforming growth factor

Contributor Information

Sihong Wu, Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Xi Yang, Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Yongliang Lou, Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Xingxing Xiao, Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Funding

This work was supported by the National Natural Science Foundation of China (grant no. 82002117), the Scientific Research Project of Wenzhou Medical University (grant no. XY2022002), and the Key Discipline of Zhejiang Province in Medical Technology (First Class, Category A).

Conflict of interests

The authors declare no conflicts of interest.

Author contributions

All authors contributed to the conception, writing, and revision of this article.

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