Segmented filamentous bacteria impede rotavirus infection via retinoic acid receptor-mediated signaling

ABSTRACTPrevention of rotavirus (RV) infection by gut-resident segmented filamentous bacteria (SFB) is an example of the influence of gut microbiota composition on enteric viral infection. Yet, the mechanism by which SFB prevents RV infection is poorly understood. A recent report that SFB colonization of germfree mice generates retinoic acid (RA) thus activating RA receptor (RAR) signaling, which protected against Citrobacter rodentium infection, prompted us to investigate whether this pathway might contribute to SFB’s protection against RV infection. Colonization of conventional mice by SFB indeed increased intestinal RA levels and direct administration of RA partially mimicked the protection against RV infection conferred by SFB. Moreover, blockade of RAR signaling eliminated SFB’s protection against RV infection. Blockade of RAR signaling did not impact RV infection in the absence of SFB, nor did it alter the protection against RV infection conferred by bacterial flagellin, which in contrast to SFB, is dependent upon IL-22 signaling. SFB/RA-mediated prevention of RV infection was associated with an RA-dependent increase in enterocyte migration, consistent with the notion that enhanced anoikis is the ultimate means by which SFB, IL-22, and RA impede RV infection.