The role of the macrophage in influenza virus
infection is complex. Macrophages are critical for resolution of influenza virus
infections but implicated in morbidity and mortality in severe
infections. They can be infected with influenza virus and consequently macrophage
infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus
infection and therefore studied the
infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers
inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following
infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following
infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus,
infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following
infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus
infection.