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Título: | Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense |
Fecha de publicación: | 2016 |
Editorial: | Nature |
Cita bibliográfica: | Nature Immunology, volumen 17, nº 9, año 2016, páginas 1037-1045. |
Materias relacionadas: | CDU::6 - Ciencias aplicadas |
Palabras clave: | Macrophage Mitochondria Infection Inflammation Cytokine |
Resumen: | The mitochondrial electron transport chain (ETC) is a metabolic hub whose adaptations accompany fuel source fluctuations, stress responses, and innate immune signals to ensure optimal cellular functions. Macrophages tightly scale their core metabolism upon activation by innate immune receptors but the precise regulation of the ETC upon pathogen recognition and its functional implications are currently unknown. Here we show that innate immune sensing of live bacteria by macrophages elicits transient ETC adaptations that is characterized by a decrease assembly of complex I (CI) and CI-containing supercomplexes and by a switch in the relative contribution of complexes I and II to mitochondrial respiration. This is mediated by the phagosomal nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and the reactive oxygen species (ROS)-dependent Src-family tyrosine-kinase Fgr and required Toll-like receptor (TLR) signalling and the NOD-like receptor (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome, both connected to bacterial viability-specific immune responses. Consistently, the inhibition of CII in E. coli infected mice decreases IL-1b and increases IL-10 serum-levels to those found in mice treated with dead bacteria and impairs control of bacteria. We thus identify the innate immune receptor-mediated ETC adaptations as an early immune-metabolic checkpoint that potentially adjusts innate immune responses during bacterial infection. |
Autor/es principal/es: | Garaude, Johan Acín-Pérez, Rebeca Martínez-Cano, Sarai Enamorado, Michael Ugolini, Matteo Nistal-Villan, Estanislao Hervás-Stubbs, Sandra Pelegrin, Pablo Sander, Leif E. Enríquez, José A. Sancho, David |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular B e Inmunología |
Versión del editor: | https://www.nature.com/articles/ni.3509 |
URI: | http://hdl.handle.net/10201/138146 |
DOI: | https://doi.org/10.1038/ni.3509 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 46 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Descripción: | ©2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted, version of a Published Work that appeared in final form in Nature Immunology. To access the final edited and published work see https://doi.org/10.1038/ni.3509 |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
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Fichero | Descripción | Tamaño | Formato | |
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suppl 2016 Nat Immunol.pdf | Versión aceptada del artículo | 8,5 MB | Adobe PDF | Visualizar/Abrir |
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