Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1

Cardiovasc Res. 2013 Aug 1;99(3):494-504. doi: 10.1093/cvr/cvt117. Epub 2013 May 13.


Aims: Atherosclerosis is a chronic inflammatory disorder of cholesterol deposition in monocyte-derived macrophages (MDM) within the arterial wall leading to impingement on the lumen of the vessel. In atherosclerotic lesions, MDM are the primary source of NADPH oxidase-derived superoxide anion (O₂⁻) inducing low-density lipoprotein (LDL) oxidation leading to their unregulated uptake of oxidized LDL and foam cell formation. We recently discovered that zymosan potently activates monocyte NADPH oxidase via the non-toll pattern recognition receptor (PRR), Dectin-1. Other PRRs bind endogenous human ligands, yet no such ligands have been identified for Dectin-1. Our hypothesis was that inflammation generates endogenous ligands for Dectin-1 that activate O₂⁻ production and thereby contributes to atherogenesis.

Methods and results: Human: anti-zymosan antibodies were used to identify similar, cross-reactive epitopes in human atherosclerotic tissue extracts. Immunoblot analysis revealed consistent antibody reactive protein bands on one- and two-dimensional gel electrophoreses. Vimentin was identified by mass spectrometry in the immunoreactive bands across different tissue samples. Direct binding of vimentin to Dectin-1 was observed using BIACORE. Further data revealed that vimentin induces O₂⁻ production by human monocytes. Analysis of human atherosclerotic lesions revealed that vimentin was detected extracellularly in the necrotic core and in areas of active inflammation. Vimentin also co-localized with Dectin-1 in macrophage-rich regions where O₂⁻ is produced.

Conclusion: We conclude that vimentin is an endogenous, activating ligand for Dectin-1. Its presence in areas of artery wall inflammation and O₂⁻ production suggests that vimentin activates Dectin-1 and contributes to the oxidation of lipids and cholesterol accumulation in atherosclerosis.

Keywords: Alarmins; Atherosclerosis; Dectin-1; Extracellular vimentin; Superoxide anion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carotid Stenosis / immunology*
  • Carotid Stenosis / metabolism*
  • Carotid Stenosis / pathology
  • Cholesterol / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Humans
  • Immunoblotting
  • Lectins, C-Type / metabolism*
  • Ligands
  • Lipid Metabolism
  • Macrophages / metabolism
  • Oxidation-Reduction
  • Protein Binding
  • Receptors, Pattern Recognition / metabolism
  • Superoxides / metabolism
  • Vimentin / metabolism*
  • Zymosan / metabolism


  • CLEC7A protein, human
  • Lectins, C-Type
  • Ligands
  • Receptors, Pattern Recognition
  • Vimentin
  • Superoxides
  • Zymosan
  • Cholesterol