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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)899-914.e7
JournalImmunity
Volume51
Issue number5
DOIs
Publication statusPublished - 2019 Nov 19
Externally publishedYes

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Keywords

  • macrophage
  • myocardial infarction
  • sepsis
  • stroke

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Hoyer, F. F., Naxerova, K., Schloss, M. J., Hulsmans, M., Nair, A. V., Dutta, P., Calcagno, D. M., Herisson, F., Anzai, A., Sun, Y., Wojtkiewicz, G., Rohde, D., Frodermann, V., Vandoorne, K., Courties, G., Iwamoto, Y., Garris, C. S., Williams, D. L., Breton, S., ... Nahrendorf, M. (2019). Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge. Immunity, 51(5), 899-914.e7. https://doi.org/10.1016/j.immuni.2019.10.010