T cells and intestinal commensal bacteria--ignorance, rejection, and acceptance

Abstract

Trillions of commensal bacteria cohabit our bodies to mutual benefit. In the past several years, it has become clear that the adaptive immune system is not ignorant of intestinal commensal bacteria, but is constantly interacting with them. For T cells, the response to commensal bacteria does not appear uniform, as certain commensal bacterial species appear to trigger effector T cells to reject and control them, whereas other species elicit Foxp3(+) regulatory T (Treg) cells to accept and be tolerant of them. Here, we review our current knowledge of T cell differentiation in response to commensal bacteria, and how this process leads to immune homeostasis in the intestine.

Keywords: Commensal; Effector cell; IgA; Inflammatory bowel disease; Intestine; Mucosa; T cell; Tolerance; Treg.

Figure 1. Mechanisms that facilitate Treg cell selection in the gut

Commensal bacteria can promote the induction of Treg cells via direct sensing of microbial products through TLRs or metabolites such as SCFAs. Commensals or SCFAs can also induce tolerogenic DCs that favor Treg cell differentiation through the production of RA and TGF-β. Mucus and intestinal WNT can also trigger a β-catenin dependent tolerogenic program in DCs. The sites of interactions are not specified in this Figure, but may be in the mesenteric lymph nodes.