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; Izabela A Rodenhuis-Zybert

doi:10.1038/s41467-020-16849-7

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

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.11(1), pp.3177-3177

06/23/2020

DOI: 10.1038/s41467-020-16849-7

PMID: 32576819

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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.

Inflammation

Capillary Permeability

Chemokines - metabolism

Child

Child, Preschool

Cytokines - metabolism

Dengue - immunology

Dengue - virology

Dengue Virus - metabolism

Endothelium, Vascular - metabolism

Female

Gene Expression Regulation

GPI-Linked Proteins - metabolism

Humans

Immunity, Innate

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

Details

Title: Subtitle: TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis
Creators: José A Aguilar-Briseño - University of Iowa, Microbiology and Immunology
Vinit Upasani - Immunology Group, Institut Pasteur du Cambodge, International Network of Pasteur Institutes, Phnom Penh, 12201, Cambodia
Bram M Ter Ellen - Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, 9700, RB, Groningen, The Netherlands
Jill Moser - Departments of Critical Care, Pathology & Medical Biology, Medical Biology section, University Medical Center Groningen, University of Groningen, 9700, RB, Groningen, The Netherlands
Mindaugas Pauzuolis - Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, 9700, RB, Groningen, The Netherlands
Mariana Ruiz-Silva - Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, 9700, RB, Groningen, The Netherlands
Sothy Heng - Kantha Bopha Hospital, Phnom Penh, 12000, Cambodia
Denis Laurent - Kantha Bopha Hospital, Phnom Penh, 12000, Cambodia
Rithy Choeung - Virology Unit, Institut Pasteur du Cambodge, International Network of Pasteur Institutes, Phnom Penh, 12201, Cambodia
Philippe Dussart - Virology Unit, Institut Pasteur du Cambodge, International Network of Pasteur Institutes, Phnom Penh, 12201, Cambodia
Tineke Cantaert - Immunology Group, Institut Pasteur du Cambodge, International Network of Pasteur Institutes, Phnom Penh, 12201, Cambodia. tcantaert@pasteur-kh.org
Jolanda M Smit - Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, 9700, RB, Groningen, The Netherlands
Izabela A Rodenhuis-Zybert - Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, 9700, RB, Groningen, The Netherlands. i.a.rodenhuis-zybert@umcg.nl
Resource Type: Journal article
Publication Details: Nature communications, Vol.11(1), pp.3177-3177
DOI: 10.1038/s41467-020-16849-7
PMID: 32576819
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: DOI: 10.13039/501100001704, name: European Society of Clinical Microbiology and Infectious Diseases; name: NWO-Veni grant
Language: English
Date published: 06/23/2020
Academic Unit: Microbiology and Immunology
Record Identifier: 9984130694902771

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