Authors

Discussion

Gut dwelling helminths infect approximately 1.45 billion people globally with children being the most infected. Chronic infection with helminths is associated with a local Th1 response regulated by the induction of immunoregulatory cytokines such as IL-10 and TGF-β. Evidence to date demonstrates that helminths themselves can encode TGF-β receptor ligands to modulate immune response and enhance their survival, although little is known about Trichuris spp. Given the impact of Trichuris as iatrogenic treatment for inflammatory diseases, we were interested to better understand the direct immunoregulatory mechanisms induced by these helminths in vivo.

Here we show that infection with Trichuris muris drives systemic host TGF-β in a dose responsive manner, independently of the adaptive immune response. Furthermore, in vivo administration of worm homogenate drives serum TGF-β in uninfected mice, demonstrating that immunoregulation is not related to intestinal damage. We demonstrate using in vitro approaches that a novel Trichuris muris homologue induces host TGF-β through interaction with the TGF-βR complex, and that this is sufficient to regulate DSS-induced colitis. These data complement and extend our current understanding of helminth immunoregulation and broaden the scope for potential therapeutics for regulation of intestinal inflammation.