Epithelial-cell-derived phospholipase A2 group 1B is an endogenous anthelminticMore about Open Access at the Crick
Authors listLewis J Entwistle Victoria S Pelly Stephanie M Coomes Yashaswini Kannan Jimena Perez-Lloret Stephanie Czieso Mariana Silva Dos Santos James MacRae Lucy Collinson Abdul Sesay Nikolay Nikolov Amina Metidji Helena Helmby David Y Hui Mark S Wilson
Immunity to intestinal helminth infections has been well studied, but the mechanism of helminth killing prior to expulsion remains unclear. Here we identify epithelial-cell-derived phospholipase A2 group 1B (PLA2g1B) as a host-derived endogenous anthelmintic. PLA2g1B is elevated in resistant mice and is responsible for killing tissue-embedded larvae. Despite comparable activities of other essential type-2-dependent immune mechanisms, Pla2g1b-/- mice failed to expel the intestinal helminths Heligmosomoides polygyrus or Nippostrongylus brasiliensis. Expression of Pla2g1b by epithelial cells was dependent upon intestinal microbiota, adaptive immunity, and common-gamma chain-dependent signaling. Notably, Pla2g1b was downregulated in susceptible mice and inhibited by IL-4R-signaling in vitro, uncoupling parasite killing from expulsion mechanisms. Resistance was restored in Pla2g1b-/- mice by treating infective H. polygyrus L3 larvae with PLA2g1B, which reduced larval phospholipid abundance. These findings uncover epithelial-cell-derived Pla2g1b as an essential mediator of helminth killing, highlighting a previously overlooked mechanism of anti-helminth immunity.
Journal Cell Host & Microbe
Issue number 4