Selective contribution of IFN-alpha/beta signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection.
A complex mechanism may be operational for dendritic cell (DC) maturation, wherein Toll-like receptor and other signaling pathways may be coordinated differently depending on the nature of the pathogens, in order for DC maturation to be most effective to a given threat. Here, we show that IFN-alpha/beta signaling is selectively required for the maturation of DCs induced by double-stranded RNA or viral infection in vitro. Interestingly, the maturation is still observed in the absence of either of the two target genes of IFN-alpha/beta, TLR3 and PKR (double-stranded-RNA-dependent protein kinase R), indicating the complexity of the IFN-alpha/beta-induced transcriptional program in DCs. We also show that the DCs stimulated in vivo by these agents can migrate into the T cell zone of the spleen but fail to mature without the IFN signal. The immune system may have acquired the selective utilization of this cytokine system, which is essential for innate antiviral immunity, to effectively couple with the induction of adaptive immunity.
Honda
Kenya
K
Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Japan.
Sakaguchi
Shinya
S
Nakajima
Chigusa
C
Watanabe
Ai
A
Yanai
Hideyuki
H
Matsumoto
Misako
M
Ohteki
Toshiaki
T
Kaisho
Tsuneyasu
T
Takaoka
Akinori
A
Akira
Shizuo
S
Seya
Tsukasa
T
Taniguchi
Tadatsugu
T
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D024202:Electrophoretic Mobility Shift Assay; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D012330:RNA, Double-Stranded / Q000502:physiology*; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology*
D017931:DNA Primers; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D016899:Interferon-beta