Editors' ChoiceHost-Pathogen Interactions

Endogenous defense against helminths

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Science Signaling  31 Oct 2017:
Vol. 10, Issue 503, eaar3224
DOI: 10.1126/scisignal.aar3224

Secreted phospholipase A2 protects against helminth infection by damaging parasite larvae.

Both cytosolic and secreted forms of phospholipase A2 (PLA2) cleave phospholipids to produce arachidonic acid, which is inflammatory and can also be metabolized to produce additional inflammatory molecules, such as eicosanoids. A study from Entwistle et al. shows that the secreted PLA2 family member PLA2g1B also defends the host against helminths. Helminth infection causes activation of type 2 immune responses, which promote inflammation, tissue repair, and physiological changes that lead to parasite expulsion (see Palma et al.). Curing mice of a primary intestinal helminth infection by treatment with an antihelminthic drug rendered the mice resistant to secondary infections. Upon secondary helminth challenge, drug-cured mice exhibited intestinal inflammation, increased expression of Pla2g1b in the intestinal epithelium, and increased PLA2 activity in the intestinal lumen. PLA2g1B knockout mice were not resistant to secondary infection, yet they retained normal type 2 immune responses. Type 2 immunity was not required for the induction of Pla2g1b expression upon secondary helminth challenge, but gut microbiota, adaptive immunity, and lymphocytes were required. Treatment with recombinant PLA2g1B reduced the phospholipid content of helminth larvae, suggesting that PLA2g1B may damage or weaken the larvae in such a way as to interfere with their development or viability. Although the details about how helminth infection induces the expression of Pla2g1b in intestinal cells are incomplete, these findings show that PLA2g1B contributes to host defense against helminths independently of the parasite expulsion processes induced by type 2 immunity and likely does so by damaging the parasite directly.

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