Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation

Abstract

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (T[subscript reg]) cell responses. However, the bacteria that induce effector T (T[subscript eff]) cells during inflammation are unclear. We addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both T[subscript reg] cell responses during homeostasis and T[subscript eff] cell responses during colitis, as suggested by an increased overlap between the T[subscript eff]/T[subscript reg] TCR repertoires with colitis. Four of six T[subscript reg] TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion of luminal Bacteroides species seen during colitis did not trigger a commensurate T[subscript eff] cell response. Unlike other T[subscript reg] cell-inducing bacteria, Helicobacter species are known pathobionts and cause disease in immunodeficient mice. Thus, our study suggests a model in which mucosal bacteria elicit context-dependent T[subscript reg] or T[subscript eff] cell responses to facilitate intestinal tolerance or inflammation. ©2017