AI Article Synopsis
- - The study reveals that type I interferons (IFNs) are crucial for controlling viral infections and preventing excessive tissue damage, known as immunopathology, which can worsen disease outcomes.
- - Researchers found that when the type I IFN receptor is absent, severe immunopathology occurs after viral infections due to macrophages and IL-6, and inhibiting these can reduce tissue damage.
- - The research highlights that macrophage-derived matrix metalloproteinases (MMPs) are involved in tissue destruction during viral infections, suggesting that targeting MMPs could be a potential treatment strategy.
Article Abstract
The ability to treat severe viral infections is limited by our understanding of the mechanisms behind virus-induced immunopathology. While the role of type I interferons (IFNs) in early control of viral replication is clear, less is known about how IFNs can regulate the development of immunopathology and affect disease outcomes. Here, we report that absence of type I IFN receptor (IFNAR) is associated with extensive immunopathology following mucosal viral infection. This pathology occurred independent of viral load or type II immunity but required the presence of macrophages and IL-6. The depletion of macrophages and inhibition of IL-6 signaling significantly abrogated immunopathology. Tissue destruction was mediated by macrophage-derived matrix metalloproteinases (MMPs), as MMP inhibition by doxycycline and Ro 28-2653 reduced the severity of tissue pathology. Analysis of post-mortem COVID-19 patient lungs also displayed significant upregulation of the expression of MMPs and accumulation of macrophages. Overall, we demonstrate that IFNs inhibit macrophage-mediated MMP production to prevent virus-induced immunopathology and uncover MMPs as a therapeutic target towards viral infections.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113601 | PMC |
| http://dx.doi.org/10.1371/journal.ppat.1010471 | DOI Listing |
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