IL-17 dependent fibroblastic reticular cell training boosts host-protective immunity to mucosal infection

Abstract Prior experience of inflammatory stimuli is thought to reduce morbidity and mortality to newly encountered infections through innate immune training that can be enhanced by childhood vaccination. Here we demonstrate that IL-17 signaling in lymph node fibroblastic reticular cells (FRC) is required for efficient clearance and protective antibody-mediated immunity to the gut bacterial pathogen Citrobacter rodentium. Furthermore, prior experience of gut inflammation led to an enhanced antibody response to C. rodentium without altering the kinetics of bacterial infection. However, colon inflammation was paradoxically reduced by previous inflammatory exposure, due to IL-10 production by B cells. Mechanistically, FRC-intrinsic IL-17 dependent activation mediated the trained response, which includes enhanced metabolic response of FRC to infection. These data identify a new pathway for immune training through FRC that modulates the adaptive response, enhancing protective antibody while reducing gut inflammation, to more efficiently preserve host health.