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

José A. Aguilar-Briseño, Vinit Upasani, Bram M. ter Ellen, Jill Moser, Mindaugas Pauzuolis, Mariana Ruiz-Silva, Sothy Heng, Denis Laurent, Rithy Choeung, Philippe Dussart, Tineke Cantaert (), Jolanda M. Smit and Izabela A. Rodenhuis-Zybert ()
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José A. Aguilar-Briseño: University of Groningen and University Medical Center Groningen
Vinit Upasani: University of Groningen and University Medical Center Groningen
Bram M. ter Ellen: University of Groningen and University Medical Center Groningen
Jill Moser: University Medical Center Groningen, University of Groningen
Mindaugas Pauzuolis: University of Groningen and University Medical Center Groningen
Mariana Ruiz-Silva: University of Groningen and University Medical Center Groningen
Sothy Heng: Kantha Bopha Hospital
Denis Laurent: Kantha Bopha Hospital
Rithy Choeung: International Network of Pasteur Institutes
Philippe Dussart: International Network of Pasteur Institutes
Tineke Cantaert: International Network of Pasteur Institutes
Jolanda M. Smit: University of Groningen and University Medical Center Groningen
Izabela A. Rodenhuis-Zybert: University of Groningen and University Medical Center Groningen

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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-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.

Date: 2020
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DOI: 10.1038/s41467-020-16849-7

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