SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset

Blood. 2011 Sep 22;118(12):e50-61. doi: 10.1182/blood-2011-01-326827. Epub 2011 Jul 29.


Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14(++)CD16(-), intermediate CD14(++)CD16(+), and nonclassical CD14(+)CD16(++) monocytes. Current knowledge on human monocyte heterogeneity is still incomplete: while it is increasingly acknowledged that CD14(++)CD16(+) monocytes are of outstanding significance in 2 global health issues, namely HIV-1 infection and atherosclerosis, CD14(++)CD16(+) monocytes remain the most poorly characterized subset so far. We therefore developed a method to purify the 3 monocyte subsets from human blood and analyzed their transcriptomes using SuperSAGE in combination with high-throughput sequencing. Analysis of 5 487 603 tags revealed unique identifiers of CD14(++)CD16(+) monocytes, delineating these cells from the 2 other monocyte subsets. Gene Ontology (GO) enrichment analysis suggests diverse immunologic functions, linking CD14(++)CD16(+) monocytes to Ag processing and presentation (eg, CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (eg, TGFB1, AIF1, PTPN6), and to angiogenesis (eg, TIE2, CD105). In conclusion, we provide genetic evidence for a distinct role of CD14(++)CD16(+) monocytes in human immunity. After CD14(++)CD16(+) monocytes have earlier been discussed as a potential therapeutic target in inflammatory diseases, we are hopeful that our data will spur further research in the field of monocyte heterogeneity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / metabolism
  • Cell Proliferation
  • Expressed Sequence Tags
  • Flow Cytometry
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation* / genetics
  • Gene Expression Regulation* / immunology
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / physiology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunity / genetics*
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Lipopolysaccharide Receptors / genetics*
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Monocytes / classification
  • Monocytes / cytology
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / immunology
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis


  • Lipopolysaccharide Receptors
  • RNA, Messenger