Immunity to Parasitic Worms

Abstract

Helminth parasites are responsible for some of the most common human infections and cause significant health problems and economic difficulties in the developing areas of the world. The type 2 immune response, characteristic of helminth infections, has been associated with the development of protective immunity and reduced worm burdens in infected humans. Further, animal model systems have demonstrated that type 2 cytokine production and signalling are necessary to promote inflammation and parasite clearance. Despite significant advances in our understanding of the mammalian immune response to helminths, the molecular and cellular mechanisms that promote type 2 immunity remain to be fully defined. Emerging studies suggest that a series of highly coordinated events including the production of epithelial cell‐derived alarmins, the activation of innate immune cells (innate lymphoid cells, haematopoietic progenitor cells, mast cells, basophils, eosinophils, neutrophils and macrophages) and the subsequent activation of lymphocytes are required to promote antihelminth immunity. This article will review these recent advances and highlight how these studies may inform the development of new therapeutic strategies to treat helminth infections and their associated morbidities.

Key Concepts

  • Helminths trigger a specific type of immune response different from that induced by microbial pathogens.
  • This response to helminths includes many of the same immune cell populations activated by microbial pathogens; however, the activation state and effector functions of the individual immune cell populations are quite different.
  • The immune cell effector functions stimulated by helminths include innate and adaptive components that mediate resistance and elimination of the parasite.
  • Effector functions of the helminth‐induced type 2 immune response also include tolerance mechanisms that mitigate tissue damage associated with trafficking of these large multicellular parasites.
  • The type 2 immune response is initiated through release of endogenous danger signals triggered by tissue damage and through release of specific parasite products that can modulate the immune response.

Keywords: type 2 immune response; alarmins; helminths; endogenous danger signals; cytokines; innate immunity; adaptive immunity

Figure 1. Cytokine alarmins produced in response to helminth parasites initiate distinct modules of innate immunity including ILC2 (a) and HSPC responses (b). ILC2s operate as potent effector cell populations capable of producing the type 2 cytokines IL‐5 and IL‐13. HSPCs are capable of differentiating into basophils and mast cells that are potent producers of the type 2 cytokine IL‐4. Collectively, these distinct pathways contribute to the development of antihelminth immunity.
Figure 2. Helminth parasites promote the production of cytokine alarmins from both epithelial cells and tissue‐resident immune cells (a). The production of cytokine alarmins promotes the expansion and activation of diverse innate immune cell populations (b) and can also have direct effects on adaptive immune cells (c). Innate and adaptive immune cells engage in cross‐talk that has been shown to amplify their effector functions (d). Collectively, innate and adaptive immune cells produce multiple effector molecules that contribute to the development of protective antihelminth immunity (e).
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Further Reading

Babu S and Nutman TB (2014) Immunology of lymphatic filariasis. Parasite Immunology 36: 338–346.

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Zaph C , Cooper PJ and Harris NL (2014) Mucosal immune responses following intestinal nematode infection. Parasite Immunology 36: 439–452.

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Siracusa, Mark C, and Gause, William C(Mar 2016) Immunity to Parasitic Worms. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000482.pub2]