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

Johan Garaude, Rebeca Acín-Pérez, Sarai Martínez-Cano, Michel Enamorado, Matteo Ugolini, Estanislao Nistal-Villán, Sandra Hervás-Stubbs, Pablo Pelegrín, Leif E. Sander, José A. Enríquez, David Sancho

Research output: Contribution to journalArticlepeer-review

219 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1037-1045
Number of pages9
JournalNature Immunology
Volume17
Issue number9
DOIs
StatePublished - 19 Aug 2016
Externally publishedYes

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