1887

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) play an important role in macrophage (MФ) development by influencing their differentiation and polarization. Our goal was to explore the difference between M-CSF- and GM-CSF-derived bone marrow MФ responsiveness to TLR7-mediated signalling pathways that influence cytokine production early after infection in a model of acute virus infection. To do so, we examined cytokine production and TLR7-mediated signalling at 1 h post-lymphocytic choriomeningitis virus (LCMV) Armstrong (ARM) infection. We found that R848-induced cytokine expression was enhanced in these cells, with GM-CSF cells exhibiting higher proinflammatory cytokine expression and M-CSF cells exhibiting higher anti-inflammatory cytokine expression. However, R848-mediated signalling molecule activation was diminished in LCMV-infected M-CSF and GM-CSF macrophages. Interestingly, we observed that TLR7 expression was maintained during LCMV infection of M-CSF and GM-CSF cells. Moreover, TLR7 expression was significantly higher in M-CSF cells compared to GM-CSF cells. Taken together, our data demonstrate that although LCMV restrains early TLR7-mediated signalling, it primes differentiated MФ to enhance expression of their respective cytokine profiles and maintains levels of TLR7 expression early after infection.

Keyword(s): cytokines , GM-CSF , M-CSF , macrophages , R848 and TLR7
Funding
This study was supported by the:
  • Faculty of Health Sciences at Queen’s University Spear and Start award
    • Principle Award Recipient: KatrinaGee
  • Natural Sciences and Engineering Research Council of Canada
    • Principle Award Recipient: KatrinaGee
  • Natural Sciences and Engineering Research Council of Canada
    • Principle Award Recipient: KatrinaGee
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/content/journal/jgv/10.1099/jgv.0.001541
2020-12-17
2021-08-02
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