Alveolar Macrophages Are the Primary Interferon-α Producer in Pulmonary Infection with RNA Viruses

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-α 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-α 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-α 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.