<i>BT1549</i> coordinates the <i>in vitro</i> IL-10 inducing activity of <i>Bacteroides thetaiotaomicron</i>

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 <i>Bacteroides thetaiotaomicron</i>, 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 <i>B. thetaiotaomicron</i>, 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 <i>BT1549</i>, a predicted secreted lipoprotein and peptidase. Collectively, our work provides insight into the molecular dialog through which <i>B. thetaiotaomicron</i> coordinates anti-inflammatory immune responses. This knowledge may facilitate future strategies to promote such responses for therapeutic purposes.