Intestinal Batf3-dependent dendritic cells are required for optimal antiviral T-cell responses in adult and neonatal mice.

Abstract

Although we know a great deal about which types of dendritic cells (DCs) promote T-cell priming in the periphery, less is known about which DC subset(s) provoke antiviral responses within the gut. Here we report that conventional Zbtb46-dependent DCs were critically required for antiviral CD8+ T-cell responses against rotavirus (RV), the major cause of childhood gastroenteritis worldwide. Furthermore, we found that in adult mice, Batf3-dependent DCs were required for generating optimal RV-specific CD8+ T-cell responses. However, in contrast to mice that lack Zbtb46-dependent DCs, a significant amount of interferon gamma-producing RV-specific CD8+ T cells were still detected in the small intestine of RV-infected adult Batf3-/- mice, suggesting the existence of compensatory cross-presentation mechanisms in the absence of Batf3-dependent DCs. In contrast to adult mice, we found that Batf3-dependent DCs were absolutely required for generating RV-specific CD8+ T-cell responses in neonates. Loss of Batf3-dependent DCs also resulted in a skewed polyclonal CD4+ T-cell response in both adult and neonatal mice upon RV infection, although local and systemic RV-specific immunoglobulin A production kinetics and titers were unimpaired. Our results provide insights that inform early-life vaccination strategies against RV infection.