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Differential production of IFN-alpha/beta by CSF-1- and GM-CSF-derived macrophages
1Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Abstract:
Mature macrophages, derived in vitro from bone marrow progenitors under the influence of either macrophage colony stimulating factor (CSF-1) or granulocyte-macrophage (GM)-CSF, have been shown to differ morphologically and functionally. The data presented in this report demonstrate that macrophages derived from bone marrow progenitors under the influence of CSF-1 are highly resistant to infection with vesicular stomatitis virus (VSV), and that this refractoriness can be reversed by treatment of cells with anti-IFN-alpha/beta antibody. In contrast, macrophages derived from bone marrow progenitors under the influence of GM-CSF are highly susceptible to the cytopathic effects of VSV, but can be protected by very low concentrations of exogenous IFN-alpha/beta. These findings suggest that CSF-1 derived macrophages have a greater capacity for the production and/or utilization of IFN-alpha/beta than GM-CSF-derived macrophages, which may account for many of the differentiative differences reported previously.
Insights
Macrophages derived with CSF-1 resist vesicular stomatitis virus (VSV) infection, while GM-CSF derived macrophages are susceptible. This difference is linked to interferon-alpha/beta (IFN-alpha/beta) production and utilization capabilities.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages are crucial immune cells with diverse functions.
- Differentiation of macrophages is influenced by colony-stimulating factors (CSFs).
- Macrophage colony-stimulating factor (CSF-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce distinct macrophage phenotypes.
Purpose of the Study:
- To investigate the differential susceptibility of CSF-1 and GM-CSF derived macrophages to vesicular stomatitis virus (VSV) infection.
- To explore the role of interferon-alpha/beta (IFN-alpha/beta) in mediating this differential susceptibility.
Main Methods:
- In vitro differentiation of bone marrow progenitors using CSF-1 or GM-CSF.
- Infection of differentiated macrophages with VSV.
- Treatment with anti-IFN-alpha/beta antibody or exogenous IFN-alpha/beta.
Main Results:
- CSF-1 derived macrophages exhibited high resistance to VSV infection.
- This resistance in CSF-1 macrophages was reversed by anti-IFN-alpha/beta antibody treatment.
- GM-CSF derived macrophages were susceptible to VSV but protected by low concentrations of exogenous IFN-alpha/beta.
Conclusions:
- CSF-1 derived macrophages possess enhanced capacity for IFN-alpha/beta production and/or utilization compared to GM-CSF derived macrophages.
- Differential IFN-alpha/beta activity contributes to the distinct functional and susceptibility profiles of CSF-1 and GM-CSF macrophages.
- These findings offer insights into macrophage differentiation and antiviral defense mechanisms.