Modulation of Specific and Allergy-Related Immune Responses by Helminths

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 species	Name	Molecule	Mechanisms of immune modulation during infection	Reference
Echinococcus granulosus	AgB	Antigen B	Reduces expression of costimulatory molecules on human DCs and induces Th2	[17]
Fasciola hepatica	FheCL1	Cysteine protease	Prevents release of macrophage inflammatory mediators by degrading TLR3	[18]
Schistosoma mansoni	Lyso-PS	Lyso-phosphatidylserine	Lyso-PS treated DCs induce IL-10^+ Treg through TLR2 and promote Th2 polarization	[19, 20]
	DsRNA	Double-stranded RNA	Triggers TLR3 to activate STAT1 and induces expression of type 1 IFNs in DCs	[21, 22]
	Omega-1	Ribonuclease	Reduces expression of costimulatory molecules and IL-12 in DCs and induces IL-4 and Foxp3 in CD4^+ cells	[23–25]
	IPSE/alpha-1	Glycoprotein	Induces IgE-dependent IL-4 production from basophils in vivo	[26]
	SmCKBP	Chemokine-binding protein	Suppresses neutrophil recruitment by inhibiting the mammalian chemokine CXCL8	[27]
Ascaris suum	PAS-1	200 kDa protein	Suppresses proinflammatory cytokines and neutrophil influx after exposure to LPS	[28]
Necator americanus	Na-ASP-2	High homology to C-C chemokines	Secreted by infective larvae, recruits neutrophils in vitro and in vivo	[29]
	Na-NES	Metalloprotease	Cleaves the eosinophil chemoattractant CCL11 and prevents its action in vitro and in vivo	[30]
Nippostrongylus brasiliensis	Acetylhydrolase	Acetylhydrolase	Inactivates mammalian platelet-activating factor, thus potentially regulating GI inflammation	[31]
Trichinella spiralis	Ts-MIF	MIF homologue	Inhibits migration of human PBMCs, similar to human MIF	[32]
Trichuris muris	43 kDa IFN-γ homologue	IFN-γ homologue	Binds to IFN-γ receptor in mice	[33]
Acanthocheilonema viteae	AvCystatin /Av17	Cysteine protease inhibitor	Downregulates T cell responses. Interferes with macrophage MAP kinase signaling pathways to induce IL-10	[34, 35]
	ES-62	Phosphorylcholine-containing glycoprotein	Reduces 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	[36–39]
Brugia malayi	Bm-ALT-1,; Bm-ALT-2	Abundant larval transcript proteins	Expression 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-2	Cysteine protease inhibitor	Blocks antigen presentation via MHC class II by interfering with asparaginyl endopeptidase	[41, 42]
	Bm-TGH-2	Homologue of TGF-β	Binds to mammalian TGF-β receptors thus potentially influencing Treg differentiation	[43]
Litomosoides sigmodontis	Ls-cystatin	Cysteine protease inhibitor	Reduces antigen-specific proliferation of spleen cells	[44]
Onchocerca volvulus	Onchocystatin	Cysteine protease inhibitor	Suppresses 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]