Type I interferon inhibition and dendritic cell activation during gammaherpesvirus respiratory infection.
The respiratory tract is a major mucosal site for microorganism entry into the body, and type I interferon (IFN) and dendritic cells constitute a first line of defense against viral infections. We have analyzed the interaction between a model DNA virus, plasmacytoid dendritic cells, and type I IFN during lung infection of mice. Our data show that murine gammaherpesvirus 68 (gammaHV68) inhibits type I IFN secretion by dendritic cells and that plasmacytoid dendritic cells are necessary for conventional dendritic cell maturation in response to gammaHV68. Following gammaHV68 intranasal inoculation, the local and systemic IFN-alpha/beta response is below detectable levels, and plasmacytoid dendritic cells are activated and recruited into the lung with a tissue distribution that differs from that of conventional dendritic cells. Our results suggest that plasmacytoid dendritic cells and type I IFN have important but independent roles during the early response to a respiratory gammaHV68 infection. gammaHV68 infection inhibits type I IFN production by dendritic cells and is a poor inducer of IFN-alpha/beta in vivo, which may serve as an immune evasion strategy.
Weslow-Schmidt
Janet L
JL
Columbus Children's Research Institute, 700 Children's Drive, Columbus, OH 43205, USA.
Jewell
Nancy A
NA
Mertz
Sara E
SE
Simas
J Pedro
JP
Durbin
Joan E
JE
Flaño
Emilio
E
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D041681:NIH 3T3 Cells; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018144:Rhadinovirus / Q000276:immunology*
D016898:Interferon-alpha; D016899:Interferon-beta; D007371:Interferon-gamma