TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis

Nat Commun. 2020 Jun 23;11(1):3177. doi: 10.1038/s41467-020-16849-7.


Vascular permeability and plasma leakage are immune-pathologies of severe dengue virus (DENV) infection, but the mechanisms underlying the exacerbated inflammation during DENV pathogenesis are unclear. Here, we demonstrate that TLR2, together with its co-receptors CD14 and TLR6, is an innate sensor of DENV particles inducing inflammatory cytokine expression and impairing vascular integrity in vitro. Blocking TLR2 prior to DENV infection in vitro abrogates NF-κB activation while CD14 and TLR6 block has a moderate effect. Moreover, TLR2 block prior to DENV infection of peripheral blood mononuclear cells prevents activation of human vascular endothelium, suggesting a potential role of the TLR2-responses in vascular integrity. TLR2 expression on CD14 + + classical monocytes isolated in an acute phase from DENV-infected pediatric patients correlates with severe disease development. Altogether, these data identify a role for TLR2 in DENV infection and provide insights into the complex interaction between the virus and innate receptors that may underlie disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capillary Permeability
  • Chemokines / metabolism
  • Child
  • Child, Preschool
  • Cytokines / metabolism
  • Dengue / immunology*
  • Dengue / virology
  • Dengue Virus / metabolism*
  • Endothelium, Vascular / metabolism
  • Female
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate
  • Inflammation
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Monocytes / metabolism*
  • NF-kappa B / metabolism
  • Receptors, IgG / metabolism
  • Severity of Illness Index
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 6


  • CD14 protein, human
  • Chemokines
  • Cytokines
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Lipopolysaccharide Receptors
  • NF-kappa B
  • Receptors, IgG
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6