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CD40 Signaling in Mice Elicits a Broad Antiviral Response Early during Acute Infection with RNA Viruses. | LitMetric

AI Article Synopsis

  • CD40 signaling in macrophages plays a crucial role in the immune response to RNA viruses, protecting against infections such as influenza A and Ebola.
  • Researchers found that stimulating CD40 signaling reduces viral levels and supports lung function, while its absence leads to increased viruses and compromised health.
  • The study highlights the potential of CD40 agonists as a new type of antiviral treatment, emphasizing the importance of macrophages and T-cells in this immune response.

Article Abstract

Macrophages are critical in the pathogenesis of a diverse group of viral pathogens, both as targets of infection and for eliciting primary defense mechanisms. Our prior in vitro work identified that CD40 signaling in murine peritoneal macrophages protects against several RNA viruses by eliciting IL-12, which stimulates the production of interferon gamma (IFN-γ). Here, we examine the role of CD40 signaling in vivo. We show that CD40 signaling is a critical, but currently poorly appreciated, component of the innate immune response using two distinct infectious agents: mouse-adapted influenza A virus (IAV, PR8) and recombinant VSV encoding the Ebola virus glycoprotein (rVSV-EBOV GP). We find that stimulation of CD40 signaling decreases early IAV titers, whereas loss of CD40 elevated early titers and compromised lung function by day 3 of infection. Protection conferred by CD40 signaling against IAV is dependent on IFN-γ production, consistent with our in vitro studies. Using rVSV-EBOV GP that serves as a low-biocontainment model of filovirus infection, we demonstrate that macrophages are a CD40-expressing population critical for protection within the peritoneum and T-cells are the key source of CD40L (CD154). These experiments reveal the in vivo mechanisms by which CD40 signaling in macrophages regulates the early host responses to RNA virus infection and highlight how CD40 agonists currently under investigation for clinical use may function as a novel class of broad antiviral treatments.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305536PMC
http://dx.doi.org/10.3390/v15061353DOI Listing

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