Commensal flagellated A4 bacteria inhibit intestinal Th2 responses through induction of innate cell TGFβ production (MUC9P.742)

Abstract

Abstract Interaction between host and microbiota maintains intestinal immune homeostasis. While commensal bacteria promotes Th1, Th17, and Tregs cells in lamina propria (LP) in the steady condition, it suppresses mucosal Th2 cells. Some specific commensal organisms have defined effects on mucosal immune function, e.g., SFB preferably promotes intestinal Th17 while certain Clostridium spp induce Tregs. However, it is still unclear whether there are specific commensal organisms down-regulating Th2 responses, and the mechanism involved. In this report, we showed that there were more LP Th2 cells in germ-free mice compared to the mice under SPF conditions. A4 bacteria, a commensal isolated from mouse cecum and produces immunodominant microbiota antigen, CBir1 flagellin, presented in intestinal lumen. In CBir1 TCR Tg mice, Th1, Th17 and Treg but not Th2 cells were present in the intestinal LP. When stimulated with CBir1 flagellin, naïve CBir1 Tg T cells differentiated into Th1, Th17 and Tregs but resisted Th2 differentiation. Aaddition of A4 bacteria, as well as pretreatment of APC with A4 bacteria, inhibited Th2 differentiation of OTII T cells stimulated with OVA and of wild-type T cells stimulated with anti-CD3 under Th2 polarizing conditions. A4 bacteria stimulated DC production of TGFβ, blockade of TGFβ abrogated A4 inhibition of Th2 cell development. Collectively, our data reveal that A4 bacteria inhibit intestinal Th2 responses through induction of innate cell production of TGFβ.