Human CD14dim Monocytes Patrol and Sense Nucleic Acids and Viruses via TLR7 and TLR8 Receptors

被引:969
作者
Cros, Jerome [2 ]
Cagnard, Nicolas [3 ]
Woollard, Kevin [1 ]
Patey, Natacha [2 ]
Zhang, Shen-Ying [4 ]
Senechal, Brigitte [2 ]
Puel, Anne [4 ]
Biswas, Subhra K. [5 ]
Moshous, Despina [6 ]
Picard, Capucine [6 ]
Jais, Jean-Philippe [3 ]
D'Cruz, David [7 ]
Casanova, Jean-Laurent [4 ,6 ,8 ,9 ]
Trouillet, Celine [1 ]
Geissmann, Frederic [1 ,2 ]
机构
[1] Kings Coll London, Div Immunol Infect & Inflammatory Dis, Ctr Mol & Cellular Biol Inflammat, London SE1 1UL, England
[2] Univ Paris 05, INSERM, U838, F-75015 Paris, France
[3] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Dept Biostat, F-75015 Paris, France
[4] Rockefeller Univ, Rockefeller Branch, Lab Human Genet Infect Dis, New York, NY 10065 USA
[5] Singapore Immunol Network, SIgN BMSI A STAR, Immunos 138648, Singapore
[6] Univ Paris 05, Hop Necker Enfants Malad, Pediat Immunohematol Unit, F-75015 Paris, France
[7] St Thomas Hosp, Kings Coll London, Louise Coote Lupus Unit, London SE1 7EH, England
[8] INSERM, Necker Branch, Lab Human Genet Infect Dis, U550, F-75015 Paris, France
[9] Univ Paris 05, Necker Med Sch, F-75015 Paris, France
基金
英国医学研究理事会;
关键词
PYOGENIC BACTERIAL-INFECTIONS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; DENDRITIC CELL PRECURSORS; NATURAL-KILLER-CELLS; BLOOD MONOCYTES; CD16(+) MONOCYTES; PROTECTIVE IMMUNITY; 6-SULFO LACNAC; IN-VIVO; SUBSETS;
D O I
10.1016/j.immuni.2010.08.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-alpha, IL-1 beta, 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.
引用
收藏
页码:375 / 386
页数:12
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