Regulation of maturation and activating potential in CD8+ versus CD8- dendritic cells following in vivo infection with vaccinia virus.
DC maturation is known to be a necessary step in the generation of an effective immune response. We have used vaccinia virus (VACV) as a model to investigate the regulation of DC subsets in vivo following infection. While a number of in vitro studies have shown that DC infected with VACV fail to undergo maturation, the effect of VACV infection on the maturation of and cytokine production by DC subsets in vivo remains less defined. We have found that following systemic infection with vaccinia virus, both CD8+ and CD8- dendritic cells are infected. The number of infected DC peaked at 6 h and was highly decreased by 24 h post-infection. In both subsets, there was evidence of generalized upregulation of costimulatory molecules. Surprisingly, this included vaccinia infected DC, suggesting the regulation of DC maturation in vivo is much more complex and likely influenced by DC extrinsic signals. However, while we observed generalized upregulation of costimulatory molecules, IL-12 production was restricted to a subset of non-infected cells in both the CD8+ and CD8- DC populations. Importantly, the control of IL-12 production was differentially dependent on MyD88 signaling. IL-12 production was ablated in the absence of MyD88 in CD8- DC, while it was unchanged in CD8+ DC. These findings provide new insights into the control of DC maturation in vivo and demonstrate that the regulation of maturation in vivo following virus infection can be differentially controlled in distinct types of DC.
Yammani
Rama D
RD
Department of Microbiology and Immunology, Room 5053, Hanes Building, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Pejawar-Gaddy
Sharmila
S
Gurley
Thaddeus C
TC
Weimer
Eric T
ET
Hiltbold
Elizabeth M
EM
Alexander-Miller
Martha A
MA
D000818:Animals; D017951:Antigen Presentation; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000821:virology*; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D014616:Vaccinia virus / Q000472:pathogenicity*
D016827:CD8 Antigens; D053594:Myeloid Differentiation Factor 88; D018664:Interleukin-12