Résumé
Myocardial infarction, stroke and sepsis trigger systemic inflammation and organism-wide complications that are difficult to manage. Here we examined the contribution of macrophages residing in vital organs to the systemic response after these injuries. We generated a comprehensive catalog of changes in macrophage number, origin and gene expression in the heart, brain, liver, kidney and lung of mice with myocardial infarction, stroke or sepsis. Predominantly fueled by heightened local proliferation, tissue macrophage numbers increased systemically. Macrophages in the same organ responded similarly to different injuries by altering expression of tissue-specific gene sets. Preceding myocardial infarction improved survival of subsequent pneumonia due to enhanced bacterial clearance, which was caused by IFNɣ priming of alveolar macrophages. Conversely, EGF receptor signaling in macrophages exacerbated inflammatory lung injury. Our data suggest that local injury activates macrophages in remote organs, and that targeting macrophages could improve resilience against systemic complications following myocardial infarction, stroke and sepsis. Hoyer, Maxerova et al. generate a comprehensive catalog of changes in macrophage number, origin and gene expression in the heart, brain, liver, kidney and lung of mice with myocardial infarction, stroke or sepsis. They find that local injury activates macrophages in remote organs and that these adaptations were damaging or protective in different settings.