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 Brown; Michael Whalen; Peter Libby; Mikael J Pittet; Kevin R King; Ralph Weissleder; Filip K Swirski; Matthias Nahrendorf

doi:10.1016/j.immuni.2019.10.010

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

Immunity. 2019 Nov 19;51(5):899-914.e7. doi: 10.1016/j.immuni.2019.10.010. Epub 2019 Nov 12.

Authors

Friedrich Felix Hoyer¹, Kamila Naxerova¹, Maximilian J Schloss¹, Maarten Hulsmans¹, Anil V Nair², Partha Dutta³, David M Calcagno⁴, Fanny Herisson¹, Atsushi Anzai¹, Yuan Sun¹, Gregory Wojtkiewicz¹, David Rohde¹, Vanessa Frodermann¹, Katrien Vandoorne¹, Gabriel Courties¹, Yoshiko Iwamoto¹, Christopher S Garris¹, David L Williams⁵, Sylvie Breton², Dennis Brown², Michael Whalen⁶, Peter Libby⁷, Mikael J Pittet¹, Kevin R King⁸, Ralph Weissleder⁹, Filip K Swirski¹, Matthias Nahrendorf¹⁰

Affiliations

¹ Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
² Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA; Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
³ Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, BST 1720.1, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
⁴ Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
⁵ Department of Surgery and Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, 178 Maple Avenue, Johnson City, TN 37614, USA.
⁶ Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, 55 Fruit Street, MA 02114, USA.
⁷ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
⁸ Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
⁹ Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
¹⁰ Center for Systems Biology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge Street, Boston, MA 02114, USA; Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Cell Count
Disease Susceptibility* / immunology
ErbB Receptors / metabolism
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Ischemia / etiology
Ischemia / metabolism
Macrophages / immunology*
Macrophages / metabolism*
Macrophages, Alveolar / immunology
Macrophages, Alveolar / metabolism
Mice
Muscle Cells / immunology
Muscle Cells / metabolism
Myocardial Infarction / etiology
Myocardial Infarction / metabolism
Organ Specificity / genetics
Organ Specificity / immunology
Pneumonia / etiology
Pneumonia / metabolism
Pneumonia / pathology

Substances

Biomarkers
EGFR protein, mouse
ErbB Receptors

Abstract

Publication types

MeSH terms

Substances

Grants and funding