title: Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses.
abstract: Type I interferons (IFNs) are critical for antiviral responses. Here we generated a knockin mouse in which green fluorescence protein (GFP) was expressed under the control of the Ifna6 promoter. Virus-induced expression of GFP recapitulated various IFN-alpha subtypes. Systemic infection of the mice with Newcastle disease virus (NDV) increased GFP(+) plasmacytoid dendritic cells (pDCs) via the Toll-like receptor system, and GFP(+) conventional dendritic cells (cDCs) and macrophages via the RIG-I-like helicase system. By contrast, lung infection with NDV led to IFN-alpha production in alveolar macrophages (AMs) and cDCs, but not in pDCs. Specific depletion of AMs caused a marked defect in the initial viral elimination in the lung. pDCs produced IFN-alpha in the absence of AM-mediated viral recognition, suggesting that pDCs function when the first defense line is broken. Thus, AMs act as a type I IFN producer that is important for the initial responses to viral infection in the lung.
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kumar
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsui
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Taro
authors.initials: T
authors.lastname: Kawai
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D000818:Animals; D007370:Interferon Type I / Q000235:genetics; D016898:Interferon-alpha / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000821:virology; D008171:Lung Diseases / Q000276:immunology / Q000821:virology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012327:RNA Virus Infections / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C472347:Ifna6 protein, mouse; D007370:Interferon Type I; D016898:Interferon-alpha