Susceptibility of bone marrow derived macrophages to influenza virus infection is dependent on macrophage phenotype

Gillian M. Campbell, Marlynne Q. Nicol, Ian Dransfield, Darren J. Shaw, Anthony A. Nash, Bernadette M. Dutia

Research output: Contribution to journalArticlepeer-review


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 have 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 proinflammatory markers inducible nitric oxide synthase (iNOS) and TNFα and TNFα expression was further up-regulated following infection. Alternatively activated macrophages express Arginase-1 and CD206, however, following infection, expression of these markers is down regulated while expression of iNOS and TNFα is 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 show that macrophage phenotype affects the inflammatory macrophage response following infection and indicate that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.
Original languageEnglish
Pages (from-to)2951-2960
JournalJournal of General Virology
Issue number10
Early online date9 Jul 2015
Publication statusPublished - 9 Jul 2015


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