Granulocyte/Macrophage Colony-Stimulating Factor-Derived Macrophages Exhibit Distinctive Early Immune Response to Lymphocytic Choriomeningitis Virus Infection

Abstract

Granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF) modulate differentiation and immune functions of macrophages (Mφ). Our aim was to evaluate how different Mφ differentiation conditions influence the Mφ response to virus infection. To address this, we differentiated bone marrow-derived Mφ in either GM-CSF or M-CSF and measured the cytokine responses to two different strains of lymphocytic choriomeningitis virus (LCMV) (clone 13; Cl13 or Armstrong; ARM). GM-CSF Mφ infected with either LCMV-ARM or -Cl13 produced more IL-6 than M-CSF Mφ, whereas M-CSF Mφ generated more IL-10 than GM-CSF Mφ. Interestingly, in M-CSF Mφ, LCMV-ARM induced more IL-10 production than Cl13. However, we could not detect any IL-12p70 or IL-23 after infection from either cell types. We also observed that GM-CSF Mφ was more efficient than M-CSF Mφ in supporting antigen-specific CD8+ T cell proliferation. Taken together, our data demonstrate that GM-CSF and M-CSF Mφ differ in how they respond to viral infection by their production of different cytokines, and their support for CD8+ T cell proliferation.