<i>Helicobacter</i> 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_reg) cell responses. However, the bacteria that induce effector T (T_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 <i>Helicobacter</i> species triggered both T_reg cell responses during homeostasis and T_eff cell responses during colitis, as suggested by an increased overlap between the T_eff/T_reg TCR repertoires with colitis. Four of six T_reg TCRs tested recognized mucosal-associated <i>Helicobacter</i> species in vitro and in vivo. By contrast, the marked expansion of luminal <i>Bacteroides</i> species seen during colitis did not trigger a commensurate T_eff cell response. Unlike other T_reg cell-inducing bacteria, <i>Helicobacter</i> species are known pathobionts and cause disease in immunodeficient mice. Thus, our study suggests a model in which mucosal bacteria elicit context-dependent T_reg or T_eff cell responses to facilitate intestinal tolerance or inflammation.