title: Cutting Edge: TLR-Dependent viral recognition along with type I IFN positive feedback signaling masks the requirement of viral replication for IFN-{alpha} production in plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (pDCs) recognize RNA virus infection via TLRs and consequently produce vast amounts of type I IFN. Because nucleic acid-sensing TLRs reside in the intracellular membrane compartment, it is presumable that pDCs do not require cytoplasmic viral replication to recognize the infection. By checking Newcastle disease virus (NDV) RNA abundance in GFP(+) and GFP(-) pDCs from Ifna6gfp mice, we found that NDV replication was not detected in IFN-producing pDCs. GFP(+) pDC was induced in response to replication-incompetent NDV. In contrast, the replication-incompetent NDV failed to induce IFN-producing pDCs in type I IFNR-deficient mice. The lack of IFNR signaling led to the replication of NDV and the subsequent RIG-I-like helicase-dependent IFN-alpha production in pDCs. These results showed that detection of viruses via TLRs together with a type I IFN feedback system circumvents the requirement for viral replication-dependent recognition in pDCs.
authors.affiliation: World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kumar
authors.forename: Shohei
authors.initials: S
authors.lastname: Koyama
authors.forename: Taro
authors.initials: T
authors.lastname: Kawai
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D025461:Feedback, Physiological; D005434:Flow Cytometry; D007370:Interferon Type I / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009522:Newcastle disease virus / Q000502:physiology; D012327:RNA Virus Infections / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D051193:Toll-Like Receptors