title: Mitochondria as Molecular Platforms Integrating Multiple Innate Immune Signalings.
abstract: The immune system of vertebrates confers protective mechanisms to the host through the sensing of stress-induced agents expressed during infection or cell stress. Among them, the first line of host defense composed of the innate immune sensing of these agents by pattern recognition receptors enables downstream adaptive immunity to be primed, mediating the body's appropriate response to clear infection and tissue damage. Mitochondria are «bacteria within» that allowed the emergence of functional eukaryotic cells by positioning themselves as the cell powerhouse and an initiator of cell death programs. It is striking to consider that such ancestral bacteria, which had to evade host defense at some point to develop evolutionary endosymbiosis, have become instrumental for the modern eukaryotic cell in alerting the immune system against various insults including infection by other pathogens. Mitochondria have indeed become critical regulators of innate immune responses to both pathogens and cell stress. They host numerous modulators, which play a direct role into the assembly of innate sensing machineries that trigger host immune response in both sterile and non-sterile conditions. Several lines of evidence indicate the existence of a complex molecular interplay between mechanisms involved in inflammation and metabolism. Mitochondrial function seems to participate in innate immunity at various stages as diverse as the transcriptional regulation of inflammatory cytokines and chemokines and their maturation by inflammasomes. Here, we review the mechanisms by which mitochondria orchestrate innate immune responses at different levels by promoting a cellular metabolic reprogramming and the cytosolic immune signaling cascades.
authors.affiliation: Bordeaux University, CIRID, 33000 Bordeaux, France; CNRS, UMR 5164, 146 rue Léo Saignat, 33076 Bordeaux, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Monlun
authors.affiliation: Bordeaux University, CIRID, 33000 Bordeaux, France; CNRS, UMR 5164, 146 rue Léo Saignat, 33076 Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hyernard
authors.affiliation: Bordeaux University, CIRID, 33000 Bordeaux, France; CNRS, UMR 5164, 146 rue Léo Saignat, 33076 Bordeaux, France; Centre Hospitalier Universitaire de Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blanco
authors.affiliation: INSERM U916, Institut Bergonié, 229 cours de l'Argonne, 33000 Bordeaux, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Lartigue
authors.affiliation: Bordeaux University, CIRID, 33000 Bordeaux, France; CNRS, UMR 5164, 146 rue Léo Saignat, 33076 Bordeaux, France. Electronic address: bfaustin@cirid.org.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Faustin
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction; D014714:Vertebrates
keywords: immunology; inflammasome; inflammation; metabolism; mitochondria