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

被引：124

作者：

Hoyer, Friedrich Felix ^{[1
,2
]}

Naxerova, Kamila ^{[1
,2
]}

Schloss, Maximilian J. ^{[1
,2
]}

Hulsmans, Maarten ^{[1
,2
]}

Nair, Anil V. ^{[1
,2
,3
,4
]}

Dutta, Partha ^{[5
,6
]}

Calcagno, David M. ^{[7
]}

Herisson, Fanny ^{[1
,2
]}

Anzai, Atsushi ^{[1
,2
]}

Sun, Yuan ^{[1
,2
]}

Wojtkiewicz, Gregory ^{[1
,2
]}

Rohde, David ^{[1
,2
]}

Frodermann, Vanessa ^{[1
,2
]}

Vandoorne, Katrien ^{[1
,2
]}

Courties, Gabriel ^{[1
,2
]}

Iwamoto, Yoshiko ^{[1
,2
]}

Garris, Christopher S. ^{[1
,2
]}

Williams, David L. ^{[8
,9
]}

Breton, Sylvie ^{[1
,2
,3
,4
]}

Brown, Dennis ^{[1
,2
,3
,4
]}

Whalen, Michael ^{[10
,11
,12
]}

Libby, Peter ^{[13
,14
]}

Pittet, Mikael J. ^{[1
,2
]}

King, Kevin R. ^{[7
,15
]}

Weissleder, Ralph ^{[1
,2
,16
]}

Swirski, Filip K. ^{[1
,2
]}

Nahrendorf, Matthias ^{[1
,2
,17
,18
,19
]}

机构：

[1] Massachusetts Gen Hosp, Dept Radiol, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA

[2] Harvard Med Sch, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA

[5] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh Heart Lung Blood & Vasc Med Inst,Div C, BST 1720-1,200 Lothrop St, Pittsburgh, PA 15213 USA

[6] Univ Pittsburgh, Med Ctr, BST 1720-1,200 Lothrop St, Pittsburgh, PA 15213 USA

[7] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[8] East Tennessee State Univ, Dept Surg, 178 Maple Ave, Johnson City, TN 37614 USA

[9] East Tennessee State Univ, Ctr Excellence Inflammat Infect Dis & Immun, 178 Maple Ave, Johnson City, TN 37614 USA

[10] Massachusetts Gen Hosp, Ctr Neurosci, 55 Fruit St, Boston, MA 02114 USA

[11] Massachusetts Gen Hosp, Dept Pediat, 55 Fruit St, Boston, MA 02114 USA

[12] Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA

[13] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA

[14] Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA

[15] Univ Calif San Diego, Dept Med, Div Cardiol, La Jolla, CA 92093 USA

[16] Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA

[17] Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA

[18] Harvard Med Sch, 185 Cambridge St, Boston, MA 02114 USA

[19] Univ Hosp Wuerzburg, Dept Internal Med 1, Wurzburg, Germany

来源：

IMMUNITY | 2019年 / 51卷 / 05期

基金：

欧盟地平线“2020”; 美国国家卫生研究院;

关键词：

CARDIAC MACROPHAGES; STEADY-STATE; ACTIVATION; MECHANISMS; STROKE; GAMMA; CELL; EXPRESSION; MICROGLIA; MONOCYTES;

D O I：

10.1016/j.immuni.2019.10.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 IFN gamma 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.

引用

页码：899 / +

页数：23

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