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

By Jerome F. Cros, N. Cagnard, K. Woollard, N. Patey, Shen-Ying Zhang, B. Senechal, A. Puel, Subhra K. Biswas, D. Moshous, C. Picard and 5 more. Immunity, 2010

1,278 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/6fa874822baef903eb60e4b854fb5b0e5c5083aa

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In Immunology

1. P. Italiani
2. D. Boraschi
3. TA Wynn
4. Steffen Jung
5. M. Guilliams
6. A. Mildner
7. P. Murray
8. F. Geissmann

Citations in the corpus

• Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, background): “Intermediate monocytes express the highest levels of antigen presentation-related molecules (18, 30) and were also shown to secrete TNF-α, IL-1β, IL-6, and CCL3 upon TLR stimulation (18, 26, 31), while Szaflarska and colleagues described an antitumoral phenotype for these cells (32).”
• Human inflammatory dendritic cells induce Th17 cell differentiation. (2013, background): “These blood cells, however, were recently shown to be a subset of CD16monocytes rather than bona fideDCs (Cros et al., 2010).”
• Monocyte recruitment during infection and inflammation (2011, background): “The CD14 + CD16 ++ subset, in terms of in vivo patrolling, is similar to the mouse LY6C low monocyte populatio”
• Inflammation and wound healing: The role of the macrophage (2011, neutral): “71 Cros, J. et al. (2010) Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7”
• Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils (2011, background): “These receptors 'instruct' macrophages to produce a variety of mediators that recruit neutrophils and promote inflammatio”
• Protective and pathogenic functions of macrophage subsets (2011, background): “, a useful characterization approach has been to quantify specific gene expression profiles after cytokine or microbial stimulatio”
• Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal (2013, background): “Notably, this response appears to be relatively specific, or at least preferential, for TLR7, given that Ly6C monocytes responded very poorly to LPS stimulation both in vitro and in vivo (Figure S2), which is in contrast to Ly6C monocytes (Figure 7F) and consistent with data in humans (Cros et al., ”
• Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases (2014, background): “Classical MC of phagocytosis, and secrete ROS and IL-10 upon LPS stimulus, wherea cytokines, TNFα and IL-1β upon inflammatory stimulation.”
• Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. (2012, background): “Ly6C monocytes, the correlate of human CD14CD16 and CD14+CD16! monocytes (Cros et al., 2010), are poised to traffic to sites of infection and inflammation (Geissmann et al.”
• Macrophages: development and tissue specialization. (2015, neutral): “Results of gene expression profiling support the alignment of the Ly6Chi and Ly6Clow mouse populations with the two main CD14+ and CD14lowCD16+ human subsets, respectively (60, 61).”
• Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. (2011, methodology): “Nonclassical monocytes were shown to exhibit patrolling behavior in vivo, and react strongly to nucleic acids and viruses.(9) But one rather surprising find was that the nonclassical subset responded poorly to lipopolysaccharide (LPS), which contradicts previous reports on the strong inflammatory re”
• From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, background): “A similar patrolling feature and TLR7/TLR8dependent reactivity were also detected in human CD14CD16 monocytes (35).”
• The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes (2018, background): “For example, classical and intermediate monocytes readily respond to bacteriaassociated signals, whereas non-classical monocytes are much less responsive (Cros et al., 2010).”
• Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis (2012, positive): “CX 3 CR1 int Ly6C + monocytes are the correlate of human CD14 + CD16 + and CD14 + CD16 − monocytes (Cros et al., 2010) and poised to traffic to sites of infection and inflammation (Geissmann et al., 2003; Serbina et al., 2008).”