Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses

作者：Kumagai Yutaro; Takeuchi Osamu; Kato Hiroki; Kumar Himanshu; Matsui Kosuke; Morii Eiichi; Aozasa Katsuyuki; Kawai Taro; Akira Shizuo^*

来源：Immunity, 2007, 27(2): 240-252.

DOI：10.1016/j.immuni.2007.07.013

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.

• 出版日期2007-8