Nat. Med. 23, 1481–1487 (2017)
The molecular drivers of myocardial infarction (MI)-driven inflammation remain unclear. In Nature Medicine, King et al. show that uptake of cellular debris by cardiac macrophages after ischemic cell death activates the production of type I interferons. Activation of the transcription factor IRF3 and induction of the cytokine- and chemokine-encoding genes Ifnb1 and Cxcl10 are detected 4 d after MI in wild-type mice but not in mice deficient in the adaptor STING or the DNA sensor cGAS. Uptake of dying cardiomyocytes by F4/80hiLy6Clo phagocytic macrophages triggers the IRF3-dependent recruitment of blood F4/80loLy6Chi pro-inflammatory monocytes that amplify the inflammatory response. Irf3–/– mice and mice deficient in the interferon receptor IFNAR are protected from death and show fewer signs of heart failure after MI. Treatment with IFNAR-neutralizing antibodies at 12 and 48 h after MI improves ventricular size, contractile function and survival in mice.
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Visan, I. Myocardial infarct inflammation. Nat Immunol 19, 99 (2018). https://doi.org/10.1038/s41590-017-0037-3
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DOI: https://doi.org/10.1038/s41590-017-0037-3