title: Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors.
abstract: Monocytes are effectors of the inflammatory response to microbes. Human CD14(+) monocytes specialize in phagocytosis and production of reactive oxygen species and secrete inflammatory cytokines in response to a broad range of microbial cues. Here, we have characterized the functions of human monocytes that lack CD14 (CD14(dim)) and express CD16. CD14(dim) monocytes were genetically distinct from natural killer cells. Gene expression analyses indicated similarities with murine patrolling Gr1(dim) monocytes, and they patrolled the endothelium of blood vessels after adoptive transfer, in a lymphocyte function-associated antigen-1-dependent manner. CD14(dim) monocytes were weak phagocytes and did not produce ROS or cytokines in response to cell-surface Toll-like receptors. Instead, they selectively produced TNF-α, IL-1β, and CCL3 in response to viruses and immune complexes containing nucleic acids, via a proinflammatory TLR7-TLR 8-MyD88-MEK pathway. Thus, CD14(dim) cells are bona fide monocytes involved in the innate local surveillance of tissues and the pathogenesis of autoimmune diseases.
authors.affiliation: U838 INSERM, Université Paris Descartes, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cros
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cagnard
authors.forename: Kevin
authors.initials: K
authors.lastname: Woollard
authors.forename: Natacha
authors.initials: N
authors.lastname: Patey
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Brigitte
authors.initials: B
authors.lastname: Senechal
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Subhra K
authors.initials: SK
authors.lastname: Biswas
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.forename: David
authors.initials: D
authors.lastname: D'Cruz
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Céline
authors.initials: C
authors.lastname: Trouillet
authors.forename: Fréderic
authors.initials: F
authors.lastname: Geissmann
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000096:biosynthesis; D058851:GPI-Linked Proteins; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D009696:Nucleic Acids / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000032:analysis; D051199:Toll-Like Receptor 7 / Q000502:physiology*; D051200:Toll-Like Receptor 8 / Q000502:physiology*; D014780:Viruses / Q000276:immunology*
chemical_list: D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009696:Nucleic Acids; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8