title: Mitochondrial DAMPs induce endotoxin tolerance in human monocytes: an observation in patients with myocardial infarction.
abstract: Monocyte exposure to mitochondrial Danger Associated Molecular Patterns (DAMPs), including mitochondrial DNA (mtDNA), induces a transient state in which these cells are refractory to further endotoxin stimulation. In this context, IRAK-M up-regulation and impaired p65 activity were observed. This phenomenon, termed endotoxin tolerance (ET), is characterized by decreased production of cytokines in response to the pro-inflammatory stimulus. We also show that monocytes isolated from patients with myocardial infarction (MI) exhibited high levels of circulating mtDNA, which correlated with ET status. Moreover, a significant incidence of infection was observed in those patients with a strong tolerant phenotype. The present data extend our current understanding of the implications of endotoxin tolerance. Furthermore, our data suggest that the levels of mitochondrial antigens in plasma, such as plasma mtDNA, should be useful as a marker of increased risk of susceptibility to nosocomial infections in MI and in other pathologies involving tissue damage.
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Fernández-Ruiz
authors.affiliation: Internal Medicine Service, Hospital La Paz, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cubillos-Zapata
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández-Jiménez
authors.affiliation: Cardiology Service, Hospital La Paz, Madrid, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Moreno-González
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Toledano
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain; Institute of Biomedical Research, Alberto Sols, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Velasco
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Vallejo-Cremades
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Esteban-Burgos
authors.affiliation: Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain; Laboratory of Immunogenetics of Diseases, IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: Rebeca Pérez
authors.initials: RP
authors.lastname: de Diego
authors.affiliation: EMPIREO Laboratory, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Llamas-Matias
authors.affiliation: Department of Mitochondrial and Neuromuscular Pathology, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Arumi
authors.affiliation: Department of Mitochondrial and Neuromuscular Pathology, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Martí
authors.affiliation: Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain; Institute of Biomedical Research, Alberto Sols, Madrid, Spain.
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
authors.affiliation: Department of Mitochondrial and Neuromuscular Pathology, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Antoni L
authors.initials: AL
authors.lastname: Andreu
authors.affiliation: Cardiology Service, Hospital La Paz, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: López-Sendón
authors.affiliation: Tumor Immunology Lab, IdiPAZ, Hospital La Paz, Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
mesh_terms: D000368:Aged; D003428:Cross Infection / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D004272:DNA, Mitochondrial / Q000097:blood*; D004731:Endotoxins / Q000097:blood* / Q000494:pharmacology; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000097:blood* / Q000473:pathology; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D004272:DNA, Mitochondrial; D004731:Endotoxins; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases