PRJNA255974
Parasitic nematodes modulate the expression of IL-17-associated genes through host type 2 immunity-dependent inhibition of segmented filamentous bacteria
Immune modulation by helminth (worm) parasites could protect the host against autoimmune diseases. We report that the parasitic nematode Nippostrongylus brasiliensis induces changes in the expression of antimicrobial peptides that are associated with marked microbial composition shifts, including reductions of segmented filamentous bacteria (SFB), a group of Gram-positive, anaerobic, spore-forming Clostridia, in ileal, jejunal, colon and fecal samples. SFB reduction correlates with decreased intestinal expression of T helper 17 (Th17) cell response markers. While infection of mice genetically deficient in the type 2 response-inducing signature cytokine IL-13 and the STAT6-activated cell signaling pathway failed to reproduce these phenotypes, administration of the type 2 response-inducing cytokine IL-25 activated a similar response in wild type mice as infection with N. brasiliensis. The reduced capacity to evoke Th17 responses resulted in increased susceptibility of N. brasiliensis-infected mice to co-infection with the bacterial pathogen Citrobacter rodentium. Our results demonstrate that helminth parasite infection alters the intestinal microbiota with SFB functioning as an immune-modulatory target for a Th17-dependent anti-inflammatory mechanism.