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Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype
Gillian M Campbell1, Marlynne Q Nicol1, Ian Dransfield2
1The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.
Abstract:
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.
Insights
Macrophage phenotype influences influenza virus infection outcomes. Alternatively activated macrophages are more susceptible to infection and viral-induced death, impacting immune responses.
Area of Science:
- Immunology
- Virology
Background:
- Macrophages play a dual role in influenza virus infections, aiding resolution but contributing to severe disease.
- Macrophage infection by influenza virus significantly impacts host immune responses.
- Macrophages exist in diverse functional states, including pro-inflammatory (classical) and anti-inflammatory (alternative) phenotypes.
Purpose of the Study:
- To investigate how different macrophage phenotypes (classical vs. alternative) respond to influenza virus infection in vitro.
- To determine the susceptibility of phenotypically distinct macrophages to influenza virus infection and subsequent cell death.
Main Methods:
- Bone marrow-derived macrophages (BMDMs) were differentiated into classical and alternative phenotypes in vitro.
- These phenotypically distinct BMDMs were infected with influenza virus.
- Expression levels of key inflammatory and regulatory markers (iNOS, TNF-α, Arginase-1, CD206) were analyzed post-infection.
Main Results:
- Alternatively activated macrophages were more readily infected and killed by influenza virus compared to classically activated macrophages.
- Influenza virus infection upregulated pro-inflammatory markers (iNOS, TNF-α) in alternatively activated macrophages, overriding their anti-inflammatory state.
- Despite upregulation, infected alternatively activated macrophages produced lower levels of pro-inflammatory markers than classically activated macrophages.
Conclusions:
- Macrophage phenotype critically influences the inflammatory response to influenza virus infection.
- Influenza virus infection can reprogram alternatively activated macrophages towards a more inflammatory state, albeit with reduced overall inflammation compared to classical macrophages.
- Modulating macrophage phenotype presents a potential therapeutic strategy for managing influenza virus infections.
