Immunomodulation and Immune Escape Strategies of Gastrointestinal Helminths and Schistosomes

Abstract

Parasitic worms (helminths) developed various immunoregulatory mechanisms to counteract the immune system of their host. The increasing identification and characterization of helminth-derived factors with strong immune modulatory activity provides novel insights into immune escape strategies of helminths. Such factors might be good targets to enhance anti-helminthic immune responses. In addition, immunosuppressive helminth-derived factors could be useful to develop new therapeutic strategies for treatment of chronic inflammatory conditions. This review will take an in depth look at the effects of immunomodulatory molecules produced by different helminths with a focus on schistosomes and mouse models of hookworm infections.

Keywords: Helminths; immunomodulation; nematode; parasites; schistosomes; trematode; type 2 immunity.

Figure 1

Major immune response pathways after helminth infection. Helminth infections induce the release of alarmins (IL-25, IL-33, TSLP) which subsequently promote immune responses that promote worm expulsion or granuloma formation but also tissue repair and immunosuppression. However, they also inhibit the IL-33 signaling pathway and modulate gene expression in monocytes/macrophages and T cells. Areg, amphiregulin; Arg-1, arginase 1; Gob5, a Calcium-activated chloride channel in goblet cells; Muc5a/c, mucins 5a and c; RELM, resistin-like molecule.

Figure 2

S. mansoni egg-derived factors with immunomodulatory activity. Overview of secreted factors from S. mansoni eggs and their action on indicated cell types. CLR, C-type lectin receptor; Cox, cyclooxygenase; PGE2, prostaglandin E2.