Intestinal Batf3-dependent dendritic cells are required for optimal antiviral T-cell responses in adult and neonatal mice.
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.
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
T
T
Sun
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
O L
OL
Rojas
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
C
C
Li
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
L A
LA
Ward
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
D J
DJ
Philpott
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
J L
JL
Gommerman
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000235:genetics; D000956:Antigens, Viral / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D005759:Gastroenteritis / Q000821:virology*; D006801:Humans; D007111:Immunity, Cellular; D007422:Intestines / Q000276:immunology* / Q000821:virology; D037181:Lectins, C-Type / Q000235:genetics; D037241:Mannose-Binding Lectins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D000956:Antigens, Viral; D050976:Basic-Leucine Zipper Transcription Factors; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D012097:Repressor Proteins; C533289:SNFT protein, mouse; D014157:Transcription Factors; C574226:Zbtb46 protein, mouse