EOH Journal Club Seminar - Spring 2017
Date: Thursday February 16, 2017
Time: 11am - 12pm
Presenter: Antonella Marrocco
Paper: Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense
Authors: 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
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.
Click Here For Article