Detalle Publicación


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

Autores: Garaude, J. (Autor de correspondencia); Acín-Pérez, R. ; Martínez-Cano, S. ; Enamorado, M. ; Ugolini, M. ; Nistal-Villán, E. ; Hervas Stubbs, Sandra; Pelegrín, P. ; Sander, L. E. ; Enríquez, J. A. (Autor de correspondencia); Sancho, D. (Autor de correspondencia)
Título de la revista: NATURE IMMUNOLOGY
ISSN: 1529-2908
Volumen: 17
Número: 9
Páginas: 1037 - 1045
Fecha de publicación: 2016
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 1ß (IL-1ß) 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.