Investigating the Role of Granulocyte Macrophage Colony Stimulating Factor in Cellular Antiviral Responses
Granulocyte macrophage colony stimulating factor (GM-CSF) is a secreted glycoprotein with many well-defined immune-modulating roles; GM-CSF recruits and promotes myeloid cell maturation and acts as a hematopoietic growth factor and proinflammatory cytokine. Amongst these functions is the ability of GM-CSF to stimulate an activated inflammatory macrophage (Mφ) phenotype, termed an M1-like Mφ. Mφ are innate immune sentinels that can adjust their phenotype according to the cytokines present in their microenvironment. The classically activated M1 Mφ, typically associated with the Th1 cytokine IFN-γ, is one of many phenotypes that Mφ can acquire, with a well-characterized role in antiviral immunity. As GM-CSF has multiple immune enhancing functions, its distant and indirect role in promoting antiviral immunity has been highlighted in the literature. However, little is known about the response of GM-CSF polarized Mφ to viral infections and whether or not GM-CSF can play a role in directly stimulating antiviral responses. To this end, we first characterized the murine Mφ cell line BMA as a model for in vitro M1-like polarization with GM-CSF (GM-Mφ). Next, we used our GM-Mφ model to investigate how Mφ activated by GM-CSF respond to virus infection. We report that GM-CSF treatment of Mφ promotes an antiviral response in these cells, whereby they show re¬sistance to viral entry, replication, and infectious progeny release compared to an untreated control Mφ (M0) phenotype. Finally, we investigated the expression of various antiviral factors that could be associated with the inhibition of viral infection/replication. The results presented in this thesis highlight the need for a better understanding of the antiviral functions that GM-CSF may have and its potential use as an antiviral to target the innate arm of immunity against emerging virus infections.
URI for this recordhttp://hdl.handle.net/1974/28919
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