the Role of CD103+ Conventional Dendritic Cells in Host Antiviral Responses in the Gut

Dendritic cells (DCs) are key modulators of the immune response. DCs are heterogeneous cells and can be divided into several subsets with unique functions. In this context, which DC subset(s) has the capacity to elicit adaptive immune responses during viral challenge at the mucosa is not fully understood. Rotavirus (RV) almost exclusively infects and replicates in the small intestinal villi, resulting in both cellular and humoral adaptive immunity. We used a RV infection mouse model to study the DC-elicited antiviral responses in the gut. By using diphtheria toxin (DT) - treated CD11c-DTR and Zbtb46-DTR chimeric mice, we demonstrated that conventional DCs (cDCs) were crucial in RV-specific CD8⁺ T cell activation and proliferation as well as RV clearance. Deficiency of CD103⁺CD11b^- cDCs (Batf3^-/- mice) can partially recapitulate the phenotype found in DT-treated Zbtb46-DTR chimeric mice, suggesting that CD103⁺CD11b^- and CD103⁺CD11b⁺ cDC subsets cooperate with each other in defending against this viral pathogen. Ongoing work is examining the RV response in huLangerin-DTA mice, whose CD103⁺CD11b⁺ cDCs are absent while CD103⁺CD11b^- cDC subset remains intact. Given the importance of RV infection in children, our future direction will focus on dissecting the role of gut DCs under RV challenge in neonatal mice.