Immunity
Volume 33, Issue 3, 24 September 2010, Pages 375-386
Journal home page for Immunity

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

https://doi.org/10.1016/j.immuni.2010.08.012Get rights and content
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Summary

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 (CD14dim) and express CD16. CD14dim monocytes were genetically distinct from natural killer cells. Gene expression analyses indicated similarities with murine patrolling Gr1dim monocytes, and they patrolled the endothelium of blood vessels after adoptive transfer, in a lymphocyte function-associated antigen-1-dependent manner. CD14dim 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, CD14dim cells are bona fide monocytes involved in the innate local surveillance of tissues and the pathogenesis of autoimmune diseases.

Highlights

► Human CD14dim monocytes patrol the vasculature ► CD14dim monocytes respond poorly to TLR1, TLR2, and TLR4 agonists ► CD14 dim monocytes respond to viruses and nucleic acids via TLR7-8-MyD88-MEK pathway

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These authors contributed equally to this work