TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis
| Autor: | Izabela A. Rodenhuis-Zybert, Vinit Upasani, Bram M. ter Ellen, Mariana Ruiz-Silva, Rithy Choeung, Jill Moser, Mindaugas Pauzuolis, Denis R. St. Laurent, Tineke Cantaert, Philippe Dussart, José Alberto Aguilar-Briseño, Sothy Heng, Jolanda M. Smit |
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| Přispěvatelé: | University of Groningen [Groningen], University Medical Center Groningen [Groningen] (UMCG), Immunologie [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Kantha Bopha Hospitals Foundation, Unité de Virologie / Virology Unit [Phnom Penh], J.A.A.B. was supported by CONACYT, Mexico. I.A.R.Z. was supported by NWO-Veni grant and the Research Grant 2019 from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). T.C. and V.U. were supported by the Institut Pasteur International Network., Translational Immunology Groningen (TRIGR), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Microbes in Health and Disease (MHD) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male MESH: Inflammation viruses Lipopolysaccharide Receptors General Physics and Astronomy MESH: Lipopolysaccharide Receptors MESH: NF-kappa B Vascular permeability MESH: Dengue Dengue virus medicine.disease_cause MESH: Monocytes MESH: Dengue Virus Severity of Illness Index Monocytes ACTIVATION Pathogenesis Dengue 0302 clinical medicine MESH: Child Child lcsh:Science MESH: Cytokines Multidisciplinary NF-kappa B virus diseases MESH: Toll-Like Receptor 2 MESH: Chemokines MESH: Toll-Like Receptor 6 MESH: Gene Expression Regulation PLATELETS RECEPTOR 2 3. Good health MESH: Leukocytes Mononuclear Child Preschool ENTRY [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Cytokines [SDV.IMM]Life Sciences [q-bio]/Immunology Female MESH: Immunity Innate MESH: Endothelium Vascular medicine.symptom Chemokines CD14 Science Inflammation MESH: Receptors IgG GPI-Linked Proteins DENDRITIC CELLS Peripheral blood mononuclear cell MATURATION General Biochemistry Genetics and Molecular Biology Virus Article Capillary Permeability 03 medical and health sciences Virology MESH: Severity of Illness Index medicine Humans MESH: Humans business.industry Receptors IgG MESH: Child Preschool MESH: Capillary Permeability General Chemistry biochemical phenomena metabolism and nutrition Immunity Innate Toll-Like Receptor 2 MESH: Male Innate immune cells TLR2 030104 developmental biology Toll-Like Receptor 6 Gene Expression Regulation Viral infection REPLICATION Immunology INNATE IMMUNITY Leukocytes Mononuclear lcsh:Q Endothelium Vascular MESH: GPI-Linked Proteins business MESH: Female RESPONSES 030215 immunology |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.3177. ⟨10.1038/s41467-020-16849-7⟩ Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications, 11(1):3177. Nature Publishing Group |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-16849-7⟩ |
| Popis: | 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. The mechanisms underlying immunpathologies in dengue virus (DENV) infection are incompletely understood. Here, authors show that TLR2 recognizes DENV particles inducing cytokine expression and activating vascular endothelium cells in vitro, and that TLR2 expression on monocytes correlates with disease severity in patients. |
| Databáze: | OpenAIRE |
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