BT1549 coordinates the in vitro IL-10 inducing activity of Bacteroides thetaiotaomicron

Abstract

Intestinal homeostasis requires the establishment of peaceful interactions between the gut microbiome and the intestinal immune system. Members of the gut microbiome, like the symbiont Bacteroides thetaiotaomicron , actively induce anti-inflammatory immune responses to maintain mutualistic relationships with the host. Despite the importance of such interactions, the specific microbial factors responsible remain largely unknown. Here, we show that B. thetaiotaomicron , which stimulates Toll-like receptor 2 (TLR2) to drive IL-10 production, can stimulate TLR2 independently of TLR1 or TLR6, the two known TLR that can form heterodimers with TLR2 to mediate TLR2-dependent responses. Furthermore, we show that IL-10 induction is likely mediated by a protease-resistant or non-proteogenic factor, and that this requires gene BT1549 , a predicted secreted lipoprotein and peptidase. Collectively, our work provides insight into the molecular dialog through which B. thetaiotaomicron coordinates anti-inflammatory immune responses. This knowledge may facilitate future strategies to promote such responses for therapeutic purposes.