Epithelial-Cell-Derived Phospholipase A2 Group 1B Is an Endogenous Anthelmintic

Publication date: 11 October 2017
Source:Cell Host & Microbe, Volume 22, Issue 4
Author(s): Lewis J. Entwistle, Victoria S. Pelly, Stephanie M. Coomes, Yashaswini Kannan, Jimena Perez-Lloret, Stephanie Czieso, Mariana Silva dos Santos, James I. 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.

Graphical abstract

Teaser

Intestinal helminths are highly prevalent in developing countries, with chronic infection causing significant host morbidity. Entwistle et al. show that epithelial-derived phospholipase A2 group 1B (PLA2g1B) acts as an endogenous anthelmintic and is essential for resistance to intestinal helminth infection via direct action on infective larvae.


http://ift.tt/2i7MQE1