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

Mucosal Immunol. 2017 May;10(3):775-788. doi: 10.1038/mi.2016.79. Epub 2016 Sep 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, CD / genetics
  • Antigens, Viral / immunology
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Child
  • Cross-Priming
  • Dendritic Cells / immunology*
  • Gastroenteritis / virology*
  • Humans
  • Immunity, Cellular
  • Intestines / immunology*
  • Intestines / virology
  • Lectins, C-Type / genetics
  • Mannose-Binding Lectins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Rotavirus / immunology*
  • Rotavirus Infections / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Antigens, CD
  • Antigens, Viral
  • Basic-Leucine Zipper Transcription Factors
  • CD207 protein, human
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Repressor Proteins
  • SNFT protein, mouse
  • Transcription Factors
  • Zbtb46 protein, mouse

Grants and funding