Virus-induced interferon alpha production by a dendritic cell subset in the absence of feedback signaling in vivo.
An effective type I interferon (IFN-alpha/beta) response is critical for the control of many viral infections. Here we show that in vesicular stomatitis virus (VSV)-infected mouse embryonic fibroblasts (MEFs) the production of IFN-alpha is dependent on type I IFN receptor (IFNAR) triggering, whereas in infected mice early IFN-alpha production is IFNAR independent. In VSV-infected mice type I IFN is produced by few cells located in the marginal zone of the spleen. Unlike other dendritic cell (DC) subsets, FACS((R))-sorted CD11c(int)CD11b(-)GR-1(+) DCs show high IFN-alpha expression, irrespective of whether they were isolated from VSV-infected IFNAR-competent or -deficient mice. Thus, VSV preferentially activates a specialized DC subset presumably located in the marginal zone to produce high-level IFN-alpha largely independent of IFNAR feedback signaling.
Barchet
Winfried
W
Mouse Biology Programme, EMBL-Monterotondo, I-00016 Monterotondo-Scalo, Rome, Italy.
Cella
Marina
M
Odermatt
Bernhard
B
Asselin-Paturel
Carine
C
Colonna
Marco
M
Kalinke
Ulrich
U
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D025461:Feedback, Physiological; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014466:Ultraviolet Rays; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*
D004268:DNA-Binding Proteins; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C494235:Irf7 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D011070:Poly I-C