Commensal A4 bacteria inhibit intestinal Th2-cell responses through induction of dendritic cell TGF-β production

Abstract

It has been shown that while commensal bacteria promote Th1, Th17 and Treg cells in lamina propria (LP) in steady-state conditions, they suppress mucosal Th2 cells. However, it is still unclear whether there are specific commensal organisms down-regulating Th2 responses, and the mechanism involved. Here we demonstrate that commensal A4 bacteria, a member of the Lachnospiraceae family, which produce an immunodominant microbiota CBir1 antigen, inhibits LP Th2-cell development. When transferred into the intestines of RAG(-/-) mice, CBir1-specific T cells developed predominately towards Th1 cells and Th17 cells, but to a lesser extent into Th2 cells. The addition of A4 bacterial lysates to CD4(+) T-cell cultures inhibited production of IL-4. A4 bacteria stimulated dendritic cell production of TGF-β, and blockade of TGF-β abrogated A4 bacteria inhibition of Th2-cell development in vitro and in vivo. Collectively, our data show that A4 bacteria inhibit Th2-cell differentiation by inducing dendritic cell production of TGF-β.

Keywords: Commensal A4 bacteria; Dendritic cell; TGF-β; Th2.