Antiviral-activated dendritic cells: a paracrine-induced response state.
Infection of immature dendritic cells (DCs) by virus stimulates their maturation into APC. Infected DCs can also expose uninfected DCs to a panoply of cytokines/chemokines via paracrine signaling. Mathematical modeling suggests that a high rate of paracrine signaling is likely to occur among DCs located in three-dimensional space. Relatively little is known about how secreted factors modify the early response to virus infection. We used a transwell experimental system that allows passage of secreted factors, but not direct contact, between virus-infected DCs and uninfected DCs to investigate paracrine signaling responses. Paracrine signaling from infected DCs induced an antiviral-primed DC state distinct from that of mature virus-infected DCs that we refer to as antiviral-activated DCs (AVDCs). AVDCs had increased surface MHC class II and CD86 levels, but in contrast to virus-infected DCs, their MHC class I levels were unchanged. Imaging flow cytometry showed that AVDCs had an increased rate of phagocytosis compared with naive DCs. Experiments with IFN-beta cytokine indicated that it may be responsible for CD86, but not MHC class II regulation in AVDCs. Both IFN-inducible and IFN-independent genes are up-regulated in AVDCs. Notably, AVDCs are relatively resistant to virus infection in comparison to naive DCs and achieve accelerated and augmented levels of costimulatory molecule expression with virus infection. AVDCs show a distinct antiviral-primed state of DC maturation mediated by DC paracrine signaling. Although further in vivo study is needed, the characteristics of the AVDC suggest that it is well suited to play a role in the early innate-adaptive transition of the immune system.
Bordería
Antonio V
AV
Department of Microbiology, Mount Sinai School of Medicine, New York, NY.
Hartmann
Boris M
BM
Department of Neurology, Mount Sinai School of Medicine, New York, NY.
Fernandez-Sesma
Ana
A
Department of Microbiology, Mount Sinai School of Medicine, New York, NY.
Moran
Thomas M
TM
Department of Microbiology, Mount Sinai School of Medicine, New York, NY.
Sealfon
Stuart C
SC
Department of Neurology, Mount Sinai School of Medicine, New York, NY.|Center for Translational Systems Biology, Mount Sinai School of Medicine, New York, NY.
D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D019899:Paracrine Communication / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D012327:RNA Virus Infections / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
D016207:Cytokines