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

作者：Garaude Johan^*; Acin Perez Rebeca; Martinez Cano Sarai; Enamorado Michel; Ugolini Matteo; Nistal Villan Estanislao; Hervas Stubbs Sandra; Pelegrin Pablo; Sander Leif E; Enriquez Jose A^*; Sancho David^*

来源：Nature Immunology, 2016, 17(9): 1037-1045.

DOI：10.1038/ni.3509

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.

• 出版日期2016-9