Mucosal Cd8 T Cell Responses Are Shaped By Batf3-Dc After Foodbornelisteria Monocytogenesinfection

While immune responses have been rigorously examined after intravenousListeria monocytogenes(Lm) infection, less is understood about its dissemination from the intestines or the induction of adaptive immunity after more physiologic models of foodborne infection. Consequently, this study focused on early events in the intestinal mucosa and draining mesenteric lymph nodes (MLN) using foodborne infection of mice withLmmodified to invade murine intestinal epithelium (InlA(M)Lm). InlA(M)Lmtrafficked intracellularly from the intestines to the MLN and were associated with Batf3-independent dendritic cells (DC) in the lymphatics. Consistent with this, InlA(M)Lminitially disseminated from the gut to the MLN normally inBatf3(-/-)mice. Activated migratory DC accumulated in the MLN by 3 days post-infection and surrounded foci of InlA(M)Lm. At this timeBatf3(-/-)mice displayed reduced InlA(M)Lmburdens, implicating cDC1 in maximal bacterial accumulation in the MLN.Batf3(-/-)mice also exhibited profound defects in the induction and gut-homing of InlA(M)Lm-specific effector CD8 T cells. Restoration of pathogen burden did not rescue antigen-specific CD8 T cell responses inBatf3(-/-)mice, indicating a critical role forBatf3in generating anti-InlA(M)Lmimmunity following foodborne infection. Collectively, these data suggest that DC play diverse, dynamic roles in the early events following foodborne InlA(M)Lminfection and in driving the establishment of intestinalLm-specific effector T cells.