C-type lectins and extracellular vesicles in virus-induced NETosis

J Biomed Sci. 2021 Jun 11;28(1):46. doi: 10.1186/s12929-021-00741-7.


Dysregulated formation of neutrophil extracellular traps (NETs) is observed in acute viral infections. Moreover, NETs contribute to the pathogenesis of acute viral infections, including those caused by the dengue virus (DV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, excessive NET formation (NETosis) is associated with disease severity in patients suffering from SARS-CoV-2-induced multiple organ injuries. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and other members of C-type lectin family (L-SIGN, LSECtin, CLEC10A) have been reported to interact with viral glycans to facilitate virus spreading and exacerbates inflammatory reactions. Moreover, spleen tyrosine kinase (Syk)-coupled C-type lectin member 5A (CLEC5A) has been shown as the pattern recognition receptor for members of flaviviruses, and is responsible for DV-induced cytokine storm and Japanese encephalomyelitis virus (JEV)-induced neuronal inflammation. Moreover, DV activates platelets via CLEC2 to release extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs). The DV-activated EXOs (DV-EXOs) and MVs (DV-MVs) stimulate CLEC5A and Toll-like receptor 2 (TLR2), respectively, to enhance NET formation and inflammatory reactions. Thus, EVs from virus-activated platelets (PLT-EVs) are potent endogenous danger signals, and blockade of C-type lectins is a promising strategy to attenuate virus-induced NETosis and intravascular coagulopathy.

Keywords: C-type lectin receptor (CLR); CLEC2; CLEC5A; COVID-19; Dengue virus (DV); Exosome (EXO); Extracellular vesicle (EV); Microvesicle (MV); Platelet; SARS-CoV-2; TLR.

Publication types

  • Review

MeSH terms

  • Blood Platelets / immunology
  • Blood Platelets / pathology
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / pathology
  • Encephalitis Virus, Japanese / immunology*
  • Encephalitis, Japanese / immunology*
  • Encephalitis, Japanese / pathology
  • Extracellular Traps / immunology*
  • Humans
  • Lectins, C-Type / immunology*
  • Platelet Activation / immunology
  • SARS-CoV-2 / immunology*
  • Signal Transduction / immunology


  • Lectins, C-Type