Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge
- PMID: 31732166
- PMCID: PMC6892583
- DOI: 10.1016/j.immuni.2019.10.010
Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge
Abstract
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.
Keywords: macrophage; myocardial infarction; sepsis; stroke.
Copyright © 2019 Elsevier Inc. All rights reserved.
Conflict of interest statement
DECLARATION OF INTERESTS
M.N. has been a paid a consultant fee or received research support from Alnylam, GSK, IFM Therapeutics, Medtronic, Molecular Imaging, Novartis, Sigilon and Verseaux.
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Comment in
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Macrophages react to remote challenges.Nat Rev Nephrol. 2020 Mar;16(3):132. doi: 10.1038/s41581-019-0236-2. Nat Rev Nephrol. 2020. PMID: 31776457 No abstract available.
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