Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

Contact

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

Abstract

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-kappaB 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.

Authors: Aguilar-BriseƱo JA, Upasani V, Ellen BMT, Moser J, Pauzuolis M, Ruiz-Silva M, Heng S, Laurent D, Choeung R, Dussart P, Cantaert T, Smit JM, Rodenhuis-Zybert IA,
Journal: Nat Commun; 2020 Jun 23 ; 11 (1) 3177. doi:10.1038/s41467-020-16849-7
Year: 2020
PubMed: PMID: 32576819 (Go to PubMed)