TY - JOUR
T1 - Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge
AU - Hoyer, Friedrich Felix
AU - Naxerova, Kamila
AU - Schloss, Maximilian J.
AU - Hulsmans, Maarten
AU - Nair, Anil V.
AU - Dutta, Partha
AU - Calcagno, David M.
AU - Herisson, Fanny
AU - Anzai, Atsushi
AU - Sun, Yuan
AU - Wojtkiewicz, Gregory
AU - Rohde, David
AU - Frodermann, Vanessa
AU - Vandoorne, Katrien
AU - Courties, Gabriel
AU - Iwamoto, Yoshiko
AU - Garris, Christopher S.
AU - Williams, David L.
AU - Breton, Sylvie
AU - Brown, Dennis
AU - Whalen, Michael
AU - Libby, Peter
AU - Pittet, Mikael J.
AU - King, Kevin R.
AU - Weissleder, Ralph
AU - Swirski, Filip K.
AU - Nahrendorf, Matthias
N1 - Funding Information:
This work was funded by the National Institutes of Health (HL139598, HL125428, NS084863, HL128264, HL129168, DP2AR075321, UL1TR001442, CA225655, GM53522, GM083016, GM119197, T32HL076136, DK57521, DK43351), the American Heart Association (AHA 17IRG33410543), the European Union's Horizon 2020 program 667837, the MGH Research Scholar Program, and the Cure Alzheimer's Fund. F.F.H. was supported by the German Research Foundation HO5279/1-2, German Heart Foundation, and the Jung Foundation for Science and Research. D.R. was supported by the German Research Foundation RO5071/1-1. F.F.H. K.N. M.J.S. M.H. A.V.N. P.D. D.M.C. G.W. D.R. V.F. K.V. G.C. Y.I. and C.S.G. conducted experiments and collected and analyzed data. F.F.H. M.J.S. F.H. A.A. and Y.S. performed surgeries. F.F.H. K.N. D.L.W. S.B. D.B. M.W. P.L. M.J.P. R.W. K.R.K. F.S. M.N. discussed results and strategy. F.F.H. K.N. and M.N. wrote the manuscript, which was edited by all co-authors. M.N. supervised, directed, and managed the study. M.N. has been paid a consultant fee or received research support from Alnylam, GSK, IFM Therapeutics, Medtronic, Molecular Imaging, Novartis, Sigilon, and Verseaux.
Funding Information:
This work was funded by the National Institutes of Health ( HL139598 , HL125428 , NS084863 , HL128264 , HL129168 , DP2AR075321 , UL1TR001442 , CA225655 , GM53522 , GM083016 , GM119197 , T32HL076136 , DK57521 , DK43351 ), the American Heart Association (AHA 17IRG33410543 ), the European Union ’s Horizon 2020 program 667837 , the MGH Research Scholar Program, and the Cure Alzheimer's Fund . F.F.H. was supported by the German Research Foundation HO5279/1-2 , German Heart Foundation , and the Jung Foundation for Science and Research . D.R. was supported by the German Research Foundation RO5071/1-1 .
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/11/19
Y1 - 2019/11/19
N2 - 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.
AB - 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.
KW - macrophage
KW - myocardial infarction
KW - sepsis
KW - stroke
UR - http://www.scopus.com/inward/record.url?scp=85074889365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074889365&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2019.10.010
DO - 10.1016/j.immuni.2019.10.010
M3 - Article
C2 - 31732166
AN - SCOPUS:85074889365
SN - 1074-7613
VL - 51
SP - 899-914.e7
JO - Immunity
JF - Immunity
IS - 5
ER -
