Table 2.
Strategies used by parasites to overcome, evade, and suppress host immunity.
| Evasion strategies | Evasion means | Example of parasites | Factor/molecule/structure/mechanism involved | Ref. |
|---|---|---|---|---|
| 1. Overcoming the hosts’ physical and physiological barriers | Skin penetration | Hookworms (Ancylostoma duodenale and Necator americanus) | Larvae enter the host through minute breaks in the skin | (Beaver, 1956; Albanese et al., 2001; Conville and Berry hill, 2007) |
| Strongyloides stercoralis | Urocanic acid, a histidine metabolite of human skin attracts the parasite lavae | (Safer et al., 2007) | ||
| Schistosoma spp. | Digest human skin elastin by using chymotrypsin-like and trypsin-like proteases | (Salter et al., 2000) | ||
| Vector and the vector’s salivary factors | Plasmodium spp. | Biting infected mosquito delivers anti-histamine, vasodialtors, anti-coagulants. platelet aggregation inhibitors, and immunomodulators | (Beier et al., 1991; Zheng et al., 2014; Gomes et al., 2016) | |
| Trypanosoma brucei | Biting Tsetse fly delivers salivary thromboregulatory compounds (5’-nucleotidase-releated apyrase, adenodine deaminase), Antigen 5, Gloss 2 peptide, and kinesin heavy chain 1 (TbKHC1) | (Caljon et al., 2009; Caljon et al., 2010; De Muylder et al., 2013; Bai et al., 2015) | ||
| Vector-induced mechanical damage | Trypanosoma cruzi | Biting wound caused by triatomine bug | (Moncayo and Yanine, 2006) | |
| Mechanical strategies to avoid immune defense mechanisms, e.g., rapid extracellular gliding motility, cell traversal motility, invasion motility | Phylum Apicomplexa, e.g., Plasmodium spp., Toxoplasma gondii | Thromospondin-related anonymous protein (TRAP), perforin-like protein (PLP1), circumsporozoite protein (CSP) | (Vanderberg, 1974; King, 1988; Mota et al., 1999; Yuda and Ishino, 2004; Kolářová, 2007; Tavares et al., 2013; Risco-Castillo et al., 2015) | |
| Resistance to serum toxic molecule; serum high density lipoproteins; trypanosome lytic factors (TLFs) | Trypanosoma brucei | Serum resistance-associated protein (SRA) | (Thomson et al., 2009) | |
| Withstanding gastric acidity |
Giardia lamblia
Entamoeba histolytica Cryptosporidium parvum |
Cysts; a significantly decreased gastric acidity and modifications of the normal microenvironmental conditions of the gastric mucosa | (Schofield et al., 1992; Striepen, 2013; Hemphill et al., 2019) | |
| Inhibit intestinal epithelial cell turnover | Giardia lamblia | Arginine deiminase | (Stadelmann et al., 2012) | |
| Breaching mucus layer | Entamoeba histolytica | Cysteine proteases and glycosidases | (Moncada et al., 2003; Lidell et al., 2006; García et al., 2015; Nakada-Tsukui and Nozaki, 2016) | |
| Digesting extracellular matrix: e.g., collagen type IV and V as well as laminin and fibronectin | Entamoeba histolytica | Many kinds of proteases | (Schulte and Scholze, 1989; Nakada-Tsukui and Nozaki, 2016) | |
| Exploit bile acid and salt | Echinococcus granulosus | Bile acids and salts help the parasite eggs to hatch in the intestine to release oncospheres that pass through the portal and lymphatic vessels and reach the liver where they usually settle and develop as larvae (metacestodes or hydatid cysts). Occasionally, the oncosperes may settle in other tissues such as brain, lung, bone and form hydatid cysts therein | (Wen et al., 2019) | |
| 2. Sequestration in the host’s immunological privileged sites | Reside in red blood cells |
Plasmodium spp. Babesia spp. |
GPI anchor surface proteins. Microneme proteins, Rhoptry proteins, peripheral surface proteins to bind to receptors on red blood cells | (Miller, 1965; David et al., 1983; Allred and Al-Khedery, 2004; Bowen and Walker, 2005; Cowman and Crabb, 2006; Bloch et al., 2019) |
| Sequestration | Plasmodium falciparum | Plasmodium falciparum erythrocyte membrane proteins (PfEMPs) | (Miller, 1965; David et al., 1983) | |
| Babesia spp. | Parasite-induced red blood cell membrane proteins | (Allred and Al-Khedery, 2004; Bloch et al., 2019) | ||
| Reside in macrophage | Leishmania spp. | Metacyclic promastigotes bind/attach to the complement receptors (CR) 1, CR3 (Mac-1), fibronectin receptor, and the mannose-fucose receptor (MR) on the surface of macrophages. Virulent L. infantum chagasi binds complement receptor 3 (CR3) but does not trigger NADPH oxidase activation and subsequent respiratory burst. On contrary, MR ligation promote inflammatory responses. The avirulent Leishmania bind both CR3 and MR. These may explain why promastigotes of virulent Leishmania spp. avoid using the MR during their invasion of macrophages and survived intracellularly. | (Wright and Silverstein, 1983; Da Silva et al., 1989; Sehgal et al., 1993; Kane and Mosser, 2000; Linehan et al., 2000; Gupta et al., 2013) | |
| Nurse cell | Trichinella spp. | Complex parasite-induced host process that involve muscle cell response (de-differentiation, cell cycle re-entry and arrest) and satellite cell responses (activation, proliferation and differentiation) | (Wu et al., 2008a) | |
| Resides in hollow organs |
Taenia spp. Ascaris lumbricoides Opisthorchis viverrini |
Avoid effective serum IgM and IgG Anti-complemenatry activity of intestine Intestinal trefoil factor (ITF) produced by goblet cells Decay accelerating factor (DAF) produced by columnar epithelial cells |
(Sun et al., 1999; Andoh et al., 2001) | |
| 3. Antigenic disguise | Merosome | Plasmodium spp. | Merozoites generated in liver cells released inside vesicles, called merosomes, into the liver sinusoid lumen. The merosomes do not express macrophage-recognition signal, such as phosphatidyl-serine, thus escape phagocytosis by kuffer cells and dendritic cells; they are carried to the lung vasculature where the merozoite cargo is released into blood stream. | (Sturn et al., 2006; Rénia and Goh, 2016; Melanie et al., 2019) |
| Camouflage with host-like/host-derived molecules | Schistosoma mansoni | Erythrocyte antigens (Rhesus, M, N, S, and Duffy), complement proteins, integrins, CD44, collagen, immunoglobulins, MHC class-I, and β2-microglobulin, | (Clegg et al., 1971; Goldring et al., 1976; Kemp et al., 1977; Snary et al., 1980; Braschi and Wilson, 2006; Braschi et al., 2006) | |
|
Schistosoma japonicum
S. mansoni |
Paramyosin (Sj97 and Sm97), Fc fragments of immunoglobulins and complements C1 and C9 proteins | (Laclette et al., 1992; Loukas et al., 2001; Deng et al., 2007) | ||
| Onchocerca volvulus | Factor H | (Meri et al., 2002) | ||
| Trypanosoma cruzi | Parasite uses trans-sialidases to transfer sialic acid from the host glycoconjugates to the parasite surface | (Nardy et al., 2016) | ||
| Echinococcus granulosus | Host cells in the pericyst | (Golzari and Sokouti, 2014) | ||
| 4. Parasites exist in different development forms | Different morphological forms/stages-specific excretory-secretory products |
Brugia malayi Schistosoma spp. Trypanosoma spp. Plasmodium spp. and many others |
Many parasite exists in different forms and shapes. They may express different sets of genes at a particular time which causes antigenic polymorphism | (Florens et al., 2002; Gryseels et al., 2006; Moreno and Geary, 2008; Fitzpatrick et al., 2009; Mitchell et al., 2012; McWilliam et al., 2013; Colley et al., 2014; Smit et al., 2015; Rénia and Goh, 2016; Reamtong et al., 2019) |
| 5. Antigenic variation | Surface antigen variation | Trypanosomatids | Variant-specific glycoproteins | (Cross, 1975; Umekita et al., 1988; Umekita et al., 1997; Pays, 2006) |
| Plasmodium spp.Babesia spp. | Antigenic variation of the relapse variants | (Cox, 1962; Brown and Brown, 1965; Hommel et al., 1983; al-Khedery et al., 1999; Winter et al., 2005; Recker et al., 2011; Rénia and Goh, 2016; Bloch et al., 2019) | ||
| 6. Antigen capping | Get rid of immune complex | Trypanosoma brucei | Flagella pockets, endosomal proteins: RAB5 and RAB11 | (Barry, 1979; Pal et al., 2003; Engstler et al., 2004) |
| Entamoeba histolytica | RAB11 | (Espinosa-Cantellano and Martínez-Palomo, 2000; Chávez-Munguía et al., 2012) | ||
| Lesihmania donovani | Stage-specific antibodies to amastigotes/promastigotes cause the parasite surface membrane antigens to aggregate, move along the longitudinal cell axis, form polar cell caps, and subsequently disappear | (Dwyer, 1976) | ||
| 7. Molecular mimicry | Complement resistance |
Schistosoma mansoni
Schistosoma haematobium |
Complement C2 receptor inhibitory trispannin (CRIT) | (Inal, 1999; Deng et al., 2003) |
| Brugia malayi | Keratinocytes periphilin-1 like protein | (Kazerounian and Aho, 2003) | ||
| Plasmodium falciparum | Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) | (Ludin et al., 2011) | ||
| Blood group-like antigens | Schistosoma japonicum | Blood group A, B, and O antigens | (Matsuse, 1956) | |
| Fasciola hepatica | Blood group A, H, and Lewis (Le) antigens | (Ben-Ismail et al., 1982) | ||
| Ascaris lumbricoides var suum, | A- and B- like blood group antigens | (Oliver-Gonzalez, 1944) | ||
| Hookworms | (Ota et al., 1954; Ota and Tadokoro, 1954) | |||
| Trichinella spiralis | Forssman antigen | (Mauss, 1941) | ||
| Echinococcus granulosus | Blood group P1 substance | (Levine et al., 1958) | ||
| Thrombospondin-mimic region | Plasmodium falciparum | Circumsporozoite protein (CSP) | (Robson et al., 1988) | |
| Myocardial cell protein mimicry | Trypanosoma cruzi | Parasite proteins that mimic myocardial cell proteins and induce autoimmunity | (Tanowitz et al., 2009) | |
| 8. Modify and/or suppress the host immunological factors/immune responses | ||||
| 8.1 Digestion of the host matrices, antimicrobial peptides, antibodies, and/or inhibition of the host factors | Digest extracellular matrix proteins | Entamoeba histolytica | Membrane-bound cysteine proteases | (Que and Reed, 2000) |
| Cleavage intestinal antimicrobial peptides | Entamoeba histolytica | Cysteine proteases | (Que and Reed, 2000) | |
| Digest human IgG | Entamoeba histolytica | Cysteine proteases | (Que and Reed, 2000) | |
| Trypanosoma cruzi | Cysteine protease, Cruzipain | (Berasain et al., 2003) | ||
| Schistosoma mansoni | pH and temperature-dependent trypsin-like endoprotease and metalloaminopeptidase Cercarial and schistosomular extracts |
(Auriault et al., 1981; Pleass et al., 2000) | ||
| Protease inhibitor | Schistosoma mansoni | Kunitz-type protease inhibitor (SmKI-1) | (Ranasinghe et al., 2015) | |
| 8.2 Resist killing by the host cells | Interfere phagocytic activity Reduce/inhibit oxidative radical production Resistance the highly toxic oxidative radicals |
Plasmodium spp. | Hemozoin | (Belachew, 2018) |
| Family Trypanosomatidae | Acid phosphatase (ACP) | (Baghaei, 2003; Navabi and Soleimanifard, 2015) | ||
| Leishmania donovani | Leishmania donovani chemotactic factor (LCF) | (Wenzel and Van Zandbergen, 2009) | ||
| Trypanosoma cruzi | A complex network of anti-oxidant enzymes: peroxidases (APX, CPX, and MPX), catalase, trypanothione reductase, and superoxide dismutases (SOD) | (Finzi et al., 2004; Piñeyro et al., 2011; Freire et al., 2017; Beltran-Hortelano et al., 2017) | ||
| Toxoplasma gondii | Cytosolic and mitochondrial superoxide dismutases, peroxiredoxins, glutathione-S-transferase, glutaredoxin, catalase, and thioredoxin reductase Programmed cell death 5 (TgPDCD5) and dense granule antigen 1 (GRA1) induce cell death |
(Ding et al., 2004; Seabra et al., 2004; Xue et al., 2017) | ||
| Entamoeba histolytica | Iron-containing superoxide dismutase (FeSOD, NADPH:flavin oxidoreductase | (Lo and Reeves, 1980; Arbo et al., 1990; Bruchhaus and Tannich, 1994; Pacheco-Yepez et al., 2014) | ||
| Neutrophil extracellular trap (NET) resistance | Leishmania infantum, L. major | 3′-nucleotidase/nuclease (3′NT/NU) | (Guimarães-Costa et al., 2014) | |
| Leishmania donovani | Lipophosphoglycan (LPG) | (Chang and Dwyer, 1976; Holm et al., 2001; Gabriel et al., 2010) | ||
| Leishmania spp. | Endonuclease (Lundep) in sand fly saliva | (Chagas et al., 2014) | ||
| Inhibits phagosome maturation | Leishmania donovani | Lipophosphoglycan (LPG), Synaptotagmin V | (Chang and Dwyer, 1976; Holm et al., 2001; Vinet et al., 2009; Gabriel et al., 2010) | |
| Dilute the detrimental effect of oxidative radicals | Leishmania amazonensis, L. mexicana | Parasitophorous vacuoles | (Wilson et al., 2008) | |
| Phagosomal membrane rupture | Trypanosoma cruzi | Trypanosome trans-sialidase | (Schenkman et al., 1992; Schenkman and Eichinger, 1993) | |
| ROS promote parasite growth | Trypanosoma cruzi | Trypanosome trans-sialidase causes phagosome rupture, facilitating the parasite accessibility to iron in cytoplasm | (Cardoso et al., 2016) | |
| Avoid cellular autophagy | Toxoplasma gondii | Micronemal proteins containing epidermal growth factor (EGF)-like domains, TgMICs: TgMIC3, TgMIC6 | (Meissner et al., 2002; Wang et al., 2009; Muniz-Feliciano et al., 2013) | |
| Killing host immune cells | Toxoplasma gondii | T. gondii-programmed cell death 5 (TgPDCD5) and dense granule antigen 1 (GRA1) | (Tsunawaki et al., 1988; Seabra et al., 2004) | |
| 8.3 Evasion of complement-mediated killing | Interfering classical pathway | Trypanosoma cruzi, Trichinella spiralis, Brugia malayi | Homologs of the vertebrate calreticulin; TcCRT, TsCRT, BmCRT, respectively | (Ferreira et al., 2004; Yadav et al., 2017) |
| Trypanosoma cruzi | Complement regulatory protein (TcCRP) or gp160 Complement C2 receptor inhibitory trispanning (TcCRIT) |
(Norris et al., 1989; Norris and Schrimpf, 1994; Cestari et al., 2008) | ||
| Schistosoma spp., Taenia solium | Paramyosin (a 94/97 kDa surface protein with an immunomodulatory property) that the parasites produce to inhibit complement C1 | (Laclette et al., 1992; Parizade et al., 1994) | ||
| Taenia taeniaformis | Analogous molecules of cobra venom factor, polyanionic proteolytic proteoglycan | (Hammerberg et al., 1976; Leid, 1977; Hammerberg and Williams, 1978a; Hammerberg and Williams, 1978b) | ||
| Interfering lectin pathway | Trypanosoma cruzi | Calreticulin; Complement C2 receptor inhibitory trispanning (TcCRIT) | (Kahn et al., 1996; Cestari et al., 2008; Sosoniuk et al., 2014) | |
| Interfering alternative pathway | Trypanosoma cruzi | Complement regulatory protein (TcCRP) or gp160, gp58/68 | (Fischer et al., 1988; Norris et al., 1989; Norris and Schrimpf, 1994) | |
| Entamoeba histolytica | Trypsin-sensitive membrane factor(s) | (Hamelmann et al., 1993) | ||
| Taenia taeniaformis | Analogous molecules of cobra venom factor, polyanionic proteolytic proteoglycan | (Hammerberg et al., 1976; Leid, 1977; Hammerberg and Williams, 1978a; Hammerberg and Williams, 1978b) | ||
| Inhibit complement amplification loop (Terminal pathway) | Trypanosoma cruzi | Hemolytically inactive fragment iC3b, Decay accelerating factor (DAF), Microvesicles | (Norris et al., 1989; Tambourgi et al., 1995; Cestari et al., 2012; Ramirez et al., 2016; Wyllie and Ramirez, 2017; Shao et al., 2019) | |
| Shed C3 products | Entamoeba histolytica | Surface-bound complement proteins | (Hamelmann et al., 1993) | |
| Resistance to complement-mediated lysis | Leishmania spp. | Major surface protease (MSP), alternately called gp63, leishmanolysin, EC3.4.24.36, and promastigote surface antigen (PSA) | (Yao et al., 2003) | |
| 8.4 B cells’ manipulations by parasites | B cell killing | Trypanosoma cruzi | Induction of the apoptosis of immature B cells in the bone marrow via prostaglandin E2 from CD11b+ myeloid cells | (Brown et al., 1992; Zuniga et al., 2005) |
| Trypanosoma brucei | VSG molecules | (Magez et al., 2011) | ||
| Generation of atypical memory B cells | Plasmodium spp. | Cysteine-rich interdomain region 1α (CIDR1α) of the erythrocyte membrane protein 1 (PfEMP1) | (Weiss et al., 2009; Scholzen and Sauerwein, 2013; Fernandez-Arias et al., 2016; Guthmiller et al., 2017; Obeng-Adjei et al., 2017; Rivera-Correa et al., 2019) | |
| Non-specific polyclonal antibody production: dilution of effective antibody, causing auto-immunity or cancer |
Babesia bovis Leishmania spp Schistosoma haematobium Trypanosoma cruzi Trypanosoma brucei |
DNA or oligodeoxynucleotides (ODNs) containing CpG motifs (CpG-ODN), Glutamate dehydrogenase (GDH) | (Fischer et al., 1981; Argov et al., 1989; Shoda et al., 2001; Bernasconi et al., 2002; Voulgari et al., 2003; Montes et al., 2006; Ossadron et al., 2006; Sakkas et al., 2008; Bryan et al., 2010) | |
| 8.5 Modification of the host cell activity and host cell killing | Trogocytosis |
Entamoeba histolytica
Naegleria fowler Balamuthia mandrillaris |
Trophozoites possess the ability to mediate contact-dependent host cell killing Amoebostome or food-cup |
(Fowler and Carter, 1965; Ravdin and Guerrant, 1980; Ravdin et al., 1980; Cooter, 2002; Shadrach et al., 2005; Ralston and Petri, 2011; Ralston et al., 2014; Ralston, 2015a; Ralston, 2015b) |
| Pore forming | E. histolytica | Pore-forming polypeptide, amebic pores | (Salata et al., 1989) | |
| Phagocytosis | E. histolytica | Gal/GalNAc-specific lectin, amebic RAB5 | (Saito-Nakano et al., 2004; Marion et al., 2005; Okada and Nozaki, 2006) | |
| 8.6 Immune complex formation | Avoid antibody-dependent cell mediated cytotoxicity (ADCC), complement-mediated lysis, antibody-mediated opsonization, phagocytisis | Echinostoma caproni | Excretory/secretory products, parasite-derived protease | (Cortés et al., 2017) |
| Brugia malayi | Immune complex forming proteins from microfilariae in blood circulation | (Reamtong et al., 2019) | ||
|
Onchocerca volvulus Schistosoma spp. |
Circulation immune complexes | (Bout et al., 1977; Smith et al., 1977; Paganelli et al., 1980; Lapa et al., 2013) | ||
| 8.7 Modulation/suppression of the host immune responses | ||||
| 8.7.1 Modification of the macrophage function | M1 Macrophage polarization | Schistosoma spp. | Schistosomal extract | (Zhu et al., 2014) |
| M2 Macrophage polarization | Schistosoma spp. | Secretory/excretory antigen from eggs | (Zhu et al., 2014) | |
| Schistosoma mansoni | Hemozoin | (Truscott et al., 2013) | ||
|
Leishmania spp. Trypanosoma spp. Plasmodium spp. |
The protozoan infections | (Vincendeau et al., 2003; Duleu et al., 2004; Stempin et al., 2004; Raes et al., 2007) | ||
| Regulatory phenotype of monocytes/suppressor macrophages | Brugia malayi | Microfilarial (Mf) lysate | (O’Regan et al., 2014) | |
| Macrophage activation | Trypanosoma brucei rhodesience | The parasite induces the release of reactive nitrogen intermediates and prostaglandin, which down-regulate proliferative responses by T cells during infection | (Schleifer and Mansfield, 1993) | |
| Antigen presentation impairment | Echinococcus multilocularis | The parasite affects CD40 and B7 costimulator expression on peritoneal macrophages of infected mice and impairs peritoneal T cell activation | (Mejri and Gottstein, 2006) | |
| 8.7.2 Manipulation of dendritic cells | Inhibit dendritic cell (DC) production |
Brugia malayi Plasmodium spp. |
Microfilarial antigen Merozoites |
(Semnani et al., 2001; Wykes et al., 2007; Mukherjee and Chauhan, 2008; Terrazas et al., 2010) |
| Induce type 2/Th2 response | Nippostrongylus brazilienzis | Excretory/secretory glycoproteins | (Balic et al., 2004) | |
| Schistosoma mansoni | Soluble egg antigens (SEAs) | (van Liempt et al., 2007) | ||
| Ecchinococcus granulosus | The parasite antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response | (Riganò et al., 2007) | ||
| Enhance IL-10 production | Plasmodium falciparum | Phagocytosed-free merozoites prevented soluble CD40 ligand-induced, phenotypic maturation of DCs and secretion of IL-12p70 but enhanced IL-10 production and primed, naive CD4+ cells to produce a high level of IL-10 compared with IFN-γ | (Mukherjee and Chauhan, 2008) | |
| Inhibit DC maturation | Plasmodium spp. | Hemazoin (malaria pigment) | (Bennett et al., 2001; Skorokhod et al., 2004; Diana et al., 2004; Skorokhod et al., 2005; MacDonald and Maizels, 2008) | |
| Toxoplasma gondii | The parasite products | |||
| Leishmania mexicana | Amastigote | |||
| Impaired DC function | Brugia malayi | ES-62 | (Semnani et al., 2001; Semnani et al., 2003; Semnani et al., 2008; Semnani and Nutman, 2004; Goodrige et al., 2005; Sponaas et al., 2006) | |
| Plasmodium spp. | Merozoite surface protein 1 (MSP1) | |||
| Plasmodium falciparum | Hemazoin | (Millington et al., 2006) | ||
| Toxoplasma gondii | Rhoptry (ROP) and dense granule (GRA) effector proteins | (Reis e Sousa et al., 1999; McKee et al., 2004; Machado et al., 2006) | ||
| Giardia lamblia | Parasite extracts enhance DC to secrete IL-10 but reduced secretion of IL-12. The cells also had reduced expression of MHC class II, CD80, and CD86 | (Kamda and Singer, 2009) | ||
| Leishmania amazonensis | Live L. amazonensis parasites, but not of soluble Leishmania antigen. The parasite caused a decrease in CD80 and CD1a expression and an increase in CD86, decreased IL-6 production | (Xin et al., 2007; Favali et al., 2007) | ||
| Leishmania donovani, L. major | Excretory-secretory antigens | (Ravest et al., 2008) | ||
| Alteration of DC phenotype | Leishmania amazonensis | Promastigotes and amastigotes | (Boggiatto et al., 2009) | |
| Inhibit DC migration |
Leishmania donovani, L. major |
Lysophosphoglycan. (LPG) | (Ponte-Sucre et al., 2001; Ato et al., 2002) | |
| 8.7.3 Exploitation of immune checkpoints | Activate immune checkpoint molecules PD1, PDL1, CTLA4, LAG-3 and TIM3 |
Plasmodium falciparum
P. vivax |
Merozoites | (Butler et al., 2011; Hafalla et al., 2012; Illingworth et al., 2013; Redmond et al., 2014; Costa et al., 2015; Goncalves-Lopes et al., 2016; Wykes and Lewin, 2018) |
|
Toxoplasma gondii
Echinococcus granulosus |
The parasite components and molecular mechanisms are not elucidated | (Bhadra et al., 2011; Wang and Gottstein, 2016; Wang et al., 2018) | ||
| 8.7.4 Induction of the regulatory cells of the immune system | ||||
| 8.7.4.1 Regulatory T cells (Tregs) | Recruitment of natural occurring Tregs (nTregs) |
Leishmania spp. Trypanosoma congolense |
The parasite components and molecular mechanisms are not elucidated | (Campanelli et al., 2006; Belkaid, 2007; Guilliams et al., 2007) |
| Induce the generation of inducible Tregs (iTregs) |
Schistosoma spp. Plasmodium spp. Anisakis simplex Heligosomoides polygyrus Trypanosoma cruzi |
The parasite components and molecular mechanisms are not elucidated | ( Cai et al., 2006; Kitagaki et al., 2006; Belkaid, 2007; Mariano et al., 2008; de Araújo et al., 2011; McSorley and Maizels, 2012; Wirthgen et al., 2018) | |
| Induce the generation of Tr1 | Onchocerca volvulus | The generated Tr1 cells display elevated amounts of CTLA-4 after stimulation, which mediates the inhibition of other T-cell functions | (Satoguina et al., 2002; Taylor et al., 2006) | |
| Induce the generation of Tr1, Th3 | Brugia malayi | TGF-beta homolog (TGH) from both adults and microfilariae | (Babu et al., 2005; Taylor et al., 2005; Babu et al., 2006; Taylor et al., 2007; Metenou et al., 2010; Wammes et al., 2012; Metenou and Nutman, 2013) | |
|
Toxoplasma gondii Leishmania spp. Trypanosoma cruzi |
TGF-beta homolog (TGH) | (Barral-Netto et al., 1992; Gazzinelli et al., 1992; Barral et al., 1993; Hunter et al., 1995; Rodrigues et al., 1998; Wilson et al., 1998; Li et al., 1999; McSorley et al., 2008) | ||
| 8.7.4.2 Regulatory B cells (Bregs) | Induction of various Bregs development, e.g., IL-10-producing CD1dhighCD5+ regulatory B cells, B10 | Schistosoma spp. | Schistosome egg antigen, glycoprotein IPSE/alpha-1 |
(Correale et al., 2008; van der Vlugt et al., 2012, Haeberlein et al., 2017) |
| Human filaria | Possibly the IgG4-producing B cells induced by the parasite infection | (van de Veen et al., 2013) | ||
|
Hymenolepis nana
Trichuris trichiura Ascaris lumbricoides Strongyloides stercoralis Enterobius vermucularis Toxoplasma gondii |
The parasite infected subjects were found to have an increased production of B‐cell-derived IL‐10 and neurotrophic factors although the parasite components are not elucidated | (Jeong et al., 2016; Haeberlein et al., 2017) |