Infection of dendritic cells by a gamma2-herpesvirus induces functional modulation.
The murine gamma-herpesvirus-68 (gammaHV68) establishes viral latency in dendritic cells (DCs). In the present study, we examined the specific consequences of DC infection by gammaHV68, both in vivo and in vitro. Ex vivo analysis of infected mice showed that the virus colonizes respiratory DCs very early after infection and that all subsets of splenic DCs analyzed are viral targets. We have developed and characterized an in vitro model of gammaHV68 infection of DCs. Using this model, we demonstrated that viral infection neither induces full DC maturation nor interferes with exogenous activation, which is assessed by cell surface phenotypic changes. However, whereas gammaHV68 infection alone failed to elicit cytokine secretion, IL-10 secretion of exogenously activated DCs was enhanced. Furthermore, gammaHV68-infected DCs efficiently stimulated virus-specific T cell hybridomas but failed to induce alloreactive stimulation of normal T cells. These data indicate that viral infection doesn't interfere with Ag processing and presentation but does interfere with the ability of DCs to activate T cells. The inhibition of T cell activation was partially reversed by blocking IL-10. Analysis of infected mice shows elevated levels of IL-10 expression in DCs and that lack of endogenous IL-10 is associated with decreased gammaHV68 long-term latency. Taken together, these observations indicate that gamma2-herpesvirus infection of DCs is a mechanism of viral immune evasion, partially mediated by IL-10.
Flaño
Emilio
E
Center for Vaccines and Immunity, Columbus Children's Research Institute, Columbus, OH 43205, USA.
Kayhan
Basak
B
Woodland
David L
DL
Blackman
Marcia A
MA
D000818:Animals; D003713:Dendritic Cells / Q000502:physiology* / Q000821:virology*; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D018144:Rhadinovirus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D017735:Virus Latency
D016753:Interleukin-10