Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense

被引：230

作者：

Garaude, Johan ^{[1
,2
]}

Acin-Perez, Rebeca ^{[1
]}

Martinez-Cano, Sarai ^{[1
]}

Enamorado, Michel ^{[1
]}

Ugolini, Matteo ^{[3
]}

Nistal-Villan, Estanislao ^{[4
,8
]}

Hervas-Stubbs, Sandra ^{[4
,5
]}

Pelegrin, Pablo ^{[6
]}

Sander, Leif E. ^{[3
]}

Enriquez, Jose A. ^{[1
,7
]}

Sancho, David ^{[1
]}

机构：

[1] Ctr Nacl Invest Cardiovasc Carlos III CNIC, Madrid, Spain

[2] INSERM, Inst Regenerat Med & Biotherapies, U1183, F-U1183 Montpellier, France

[3] Charite Hosp Berlin, Dept Infect Dis & Pulm Med, Berlin, Germany

[4] Univ Navarra, Ctr Invest Med Aplicada, Pamplona, Spain

[5] Recinto Complejo Hosp Navarra, Inst Invest Sanitaria Navarra IDISNA, Pamplona, Spain

[6] Hosp Clin Univ Virgen Arrixaca, Unidad Inflamac & Cirugia Expt, Ctr Invest Biomed Red Area Temat Enfermedades Hep, Inst Murciano Invest Biosanitaria Arrixaca, Murcia, Spain

[7] Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, Zaragoza, Spain

[8] Univ CEU San Pablo, Microbiol Sect, Dept Pharmaceut & Hlth Sci, Fac Pharm, Madrid, Spain

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 09期

基金：

欧盟地平线“2020”;

关键词：

COMPLEX-I; INNATE; DEHYDROGENASE; SUCCINATE; CELL; ACTIVATION; CASPASE-1; IL-1-BETA; INDUCTION; KINASES;

D O I：

10.1038/ni.3509

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Macrophages tightly scale their core metabolism after being activated, but the precise regulation of the mitochondrial electron-transport chain (ETC) and its functional implications are currently unknown. Here we found that recognition of live bacteria by macrophages transiently decreased assembly of the ETC complex I (CI) and Cl-containing super-complexes and switched the relative contributions of CI and CII to mitochondria! respiration. This was mediated by phagosomal NADPH oxidase and the reactive oxygen species (ROS)-dependent tyrosine kinase Fgr. It required Toll-like receptor signaling and the NLRP3 inflammasome, which were both connected to bacterial viability specific immune responses. Inhibition of CII during infection with Escherichia coli normalized serum concentrations of interleukin 1 beta (IL-1 beta) and IL-10 to those in mice treated with dead bacteria and impaired control of bacteria. We have thus identified ETC adaptations as an early immunological-metabolic checkpoint that adjusts innate immune responses to bacterial infection.

引用

页码：1037 / 1045

页数：9

共 41 条

[41] TLR signalling augments macrophage bactericidal activity through mitochondrial ROS [J].

West, A. Phillip ;

Brodsky, Igor E. ;

Rahner, Christoph ;

Woo, Dong Kyun ;

Erdjument-Bromage, Hediye ;

Tempst, Paul ;

Walsh, Matthew C. ;

Choi, Yongwon ;

Shadel, Gerald S. ;

Ghosh, Sankar .

NATURE, 2011, 472 (7344) :476-U543

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