The gut microbiota limits Th2 immunity to Heligmosomoides polygyrus bakeri infection

Abstract

Helminth-induced alterations to the gut microbiota have been shown to affect immune responses at local and peripheral sites. Studies examining helminth-microbiota interactions, however, have been limited due to the practical constraints of performing germ-free experiments with parasites that thrive in microbial-rich conditions to complete their development. The infectious (L3) larvae of the murine helminth Heligmosomoides polygyrus bakeri (Hpb), for example, are normally reared using a fecal-culture method and therefore are inherently unsuitable for germ-free studies in vivo. Herein, we detail an adapted methodology for rearing effectively germ-free Hpb larvae that are able to maintain the axenic status of a germ-free host during infection. We validate that these larvae do not display any fitness defects relative to fecal-grown larvae and evoke a comparable immune response in vivo. Characterization of axenic Hpb infection reveals that the commensal microbiota play a multifaceted role during infection - curbing the anti-Hpb Th2 response and directing the resolution of tissue granulomas, while simultaneously promoting parasite fitness. Overall these data demonstrate a mutualistic relationship between commensal microbes, enteric helminths and the infected host.