Table 1: Helminth-derived immunomodulatory and Th2-inducing molecules. CXCL: chemokine ligand; DC: dendritic cell; Ig: immunoglobulin; GI: gastrointestinal; IFN-γ: interferon gamma; IL: interleukin; LPS: lipopolysaccharide; MAP: mitogen activated kinase; MHC: major histocompatibility complex; MIF: macrophage migration inhibitory factor; PBMC: peripheral blood mononuclear cell; STAT: signal transducer and activator of transcription; TGF: transforming growth factor; Th: T helper cell; TLR: Toll-like receptor; Treg: T regulatory cell.

Helminth speciesNameMoleculeMechanisms of immune modulation during infectionReference

Echinococcus granulosusAgBAntigen BReduces expression of costimulatory molecules on human DCs and induces Th2 [17]

Fasciola hepaticaFheCL1Cysteine proteasePrevents release of macrophage inflammatory mediators by degrading TLR3 [18]

Schistosoma mansoniLyso-PSLyso-phosphatidylserineLyso-PS treated DCs induce IL-10+ Treg through TLR2 and promote Th2 polarization [19, 20]
DsRNADouble-stranded RNATriggers TLR3 to activate STAT1 and induces expression of type 1 IFNs in DCs [21, 22]
Omega-1RibonucleaseReduces expression of costimulatory molecules and IL-12 in DCs and induces IL-4 and Foxp3 in CD4+ cells [2325]
IPSE/alpha-1GlycoproteinInduces IgE-dependent IL-4 production from basophils in vivo [26]
SmCKBPChemokine-binding proteinSuppresses neutrophil recruitment by inhibiting the mammalian chemokine CXCL8 [27]

Ascaris suumPAS-1200 kDa proteinSuppresses proinflammatory cytokines and neutrophil influx after exposure to LPS[28]

Necator americanusNa-ASP-2High homology to C-C chemokinesSecreted by infective larvae, recruits neutrophils in vitro and in vivo [29]
Na-NESMetalloproteaseCleaves the eosinophil chemoattractant CCL11 and prevents its action in vitro and in vivo [30]

Nippostrongylus brasiliensisAcetylhydrolaseAcetylhydrolaseInactivates mammalian platelet-activating factor, thus potentially regulating GI inflammation[31]

Trichinella spiralisTs-MIFMIF homologueInhibits migration of human PBMCs, similar to human MIF [32]

Trichuris muris43 kDa IFN-γ homologueIFN-γ homologueBinds to IFN-γ receptor in mice[33]

Acanthocheilonema viteaeAvCystatin /Av17Cysteine protease inhibitorDownregulates T cell responses. Interferes with macrophage MAP kinase signaling pathways to induce IL-10 [34, 35]
ES-62Phosphorylcholine-containing glycoproteinReduces CD4+ T cell proliferation and IL-2 production, inhibits IL-4 and IL-13 production Inhibits IL-12 production from macrophages after exposure to LPS in a TLR4-dependent manner Induces an anti-inflammatory phenotype in DCs[3639]

Brugia malayiBm-ALT-1,
Bm-ALT-2
Abundant larval transcript proteinsExpression of Bm-ALT in recombinant Leishmania mexicana parasites diminishes IFN-γ-mediated killing and induces GATA-3 and SOCS-1 in these macrophages[40]
Bm-CPI-2Cysteine protease inhibitorBlocks antigen presentation via MHC class II by interfering with asparaginyl endopeptidase [41, 42]
Bm-TGH-2Homologue of TGF-βBinds to mammalian TGF-β receptors thus potentially influencing Treg differentiation [43]

Litomosoides sigmodontisLs-cystatinCysteine protease inhibitorReduces antigen-specific proliferation of spleen cells [44]

Onchocerca volvulusOnchocystatinCysteine protease inhibitorSuppresses antigen-specific proliferation of PBMCs, induces IL-10 from stimulated PBMCs
Reduces expression of MHC class II molecules and CD86 on human monocytes
[45, 46]