Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge

Friedrich Felix Hoyer, Kamila Naxerova, Maximilian J. Schloss, Maarten Hulsmans, Anil V. Nair, Partha Dutta, David M. Calcagno, Fanny Herisson, Atsushi Anzai, Yuan Sun, Gregory Wojtkiewicz, David Rohde, Vanessa Frodermann, Katrien Vandoorne, Gabriel Courties, Yoshiko Iwamoto, Christopher S. Garris, David L. Williams, Sylvie Breton, Dennis BrownMichael Whalen, Peter Libby, Mikael J. Pittet, Kevin R. King, Ralph Weissleder, Filip K. Swirski, Matthias Nahrendorf

研究成果: Article査読

23 被引用数 (Scopus)

抄録

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, Naxerova, 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.

本文言語English
ページ(範囲)899-914.e7
ジャーナルImmunity
51
5
DOI
出版ステータスPublished - 2019 11 19
外部発表はい

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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