Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors.
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.
Cros
Jérôme
J
U838 INSERM, Université Paris Descartes, Paris, France.
Cagnard
Nicolas
N
Woollard
Kevin
K
Patey
Natacha
N
Zhang
Shen-Ying
SY
Senechal
Brigitte
B
Puel
Anne
A
Biswas
Subhra K
SK
Moshous
Despina
D
Picard
Capucine
C
Jais
Jean-Philippe
JP
D'Cruz
David
D
Casanova
Jean-Laurent
JL
Trouillet
Céline
C
Geissmann
Fréderic
F
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*
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