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Nat Immunol. 2016 Sep;17(9):1037-1045. doi: 10.1038/ni.3509. Epub 2016 Jun 27.

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

Author information

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Institute for Regenerative Medicine and Biotherapies, Institut National pour la Santé et la Recherche Médicale, U1183, Montpellier, France.
Department of Infectious Diseases and Pulmonary Medicine, Charité Hospital Berlin, Berlin, Germany.
Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Spain.
Instituto de Investigación Sanitaria de Navarra (IDISNA), Recinto de Complejo Hospitalario de Navarra, Pamplona, Spain.
Unidad de Inflamación y Cirugía Experimental, Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria-Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
Contributed equally


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 CI-containing super-complexes and switched the relative contributions of CI and CII to mitochondrial 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 1β (IL-1β) 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.

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