Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection

Dengue virus infection results in a broad spectrum of diseases ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Hitherto, there is no consensus biomarker for the prediction of severe dengue disease in patients. Yet, early identification of...

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Main Authors: Vinit Upasani, Bram M. ter Ellen, Sotheary Sann, Sokchea Lay, Sothy Heng, Denis Laurent, Sowath Ly, Veasna Duong, Philippe Dussart, Jolanda M. Smit, Tineke Cantaert, Izabela A. Rodenhuis-Zybert
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023044730
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author Vinit Upasani
Bram M. ter Ellen
Sotheary Sann
Sokchea Lay
Sothy Heng
Denis Laurent
Sowath Ly
Veasna Duong
Philippe Dussart
Jolanda M. Smit
Tineke Cantaert
Izabela A. Rodenhuis-Zybert
author_facet Vinit Upasani
Bram M. ter Ellen
Sotheary Sann
Sokchea Lay
Sothy Heng
Denis Laurent
Sowath Ly
Veasna Duong
Philippe Dussart
Jolanda M. Smit
Tineke Cantaert
Izabela A. Rodenhuis-Zybert
author_sort Vinit Upasani
collection DOAJ
description Dengue virus infection results in a broad spectrum of diseases ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Hitherto, there is no consensus biomarker for the prediction of severe dengue disease in patients. Yet, early identification of patients who progress to severe dengue is pivotal for better clinical management. We have recently reported that an increased frequency of classical (CD14 ++CD16−) monocytes with sustained high TLR2 expression in acutely infected dengue patients correlates with severe dengue development. Here, we hypothesized that the relatively lower TLR2 and CD14 expression in mild dengue patients is due to the shedding of their soluble forms (sTLR2 and sCD14) and that these could be used as indicators of disease progression. Therefore, using commercial sandwich ELISAs, we evaluated the release of sTLR2 and sCD14 by peripheral blood mononuclear cells (PBMCs) in response to in vitro dengue virus (DENV) infection and assessed their levels in acute-phase plasma of 109 dengue patients. We show that while both sTLR2 and sCD14 are released by PBMCs in response to DENV infection in vitro, their co-circulation in an acute phase of the disease is not always apparent. In fact, sTLR2 was found only in 20% of patients irrespective of disease status. In contrast, sCD14 levels were detected in all patients and were significantly elevated in DF patients when compared to DHF patients and age-matched healthy donors. Altogether, our results suggest that sCD14 may help in identifying patients at risk of severe dengue at hospital admittance.
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spelling doaj.art-6571c78510974df5859a2edda28959b52023-06-24T05:18:06ZengElsevierHeliyon2405-84402023-06-0196e17265Characterization of soluble TLR2 and CD14 levels during acute dengue virus infectionVinit Upasani0Bram M. ter Ellen1Sotheary Sann2Sokchea Lay3Sothy Heng4Denis Laurent5Sowath Ly6Veasna Duong7Philippe Dussart8Jolanda M. Smit9Tineke Cantaert10Izabela A. Rodenhuis-Zybert11Immunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia; Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, NetherlandsDepartment of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, NetherlandsImmunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, CambodiaImmunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, CambodiaKantha Bopha Children Hospital, Phnom Penh, CambodiaKantha Bopha Children Hospital, Phnom Penh, CambodiaEpidemiology and Public Health Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, CambodiaVirology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, CambodiaVirology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, CambodiaDepartment of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, NetherlandsImmunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia; Corresponding author.Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, Netherlands; Corresponding author.Dengue virus infection results in a broad spectrum of diseases ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Hitherto, there is no consensus biomarker for the prediction of severe dengue disease in patients. Yet, early identification of patients who progress to severe dengue is pivotal for better clinical management. We have recently reported that an increased frequency of classical (CD14 ++CD16−) monocytes with sustained high TLR2 expression in acutely infected dengue patients correlates with severe dengue development. Here, we hypothesized that the relatively lower TLR2 and CD14 expression in mild dengue patients is due to the shedding of their soluble forms (sTLR2 and sCD14) and that these could be used as indicators of disease progression. Therefore, using commercial sandwich ELISAs, we evaluated the release of sTLR2 and sCD14 by peripheral blood mononuclear cells (PBMCs) in response to in vitro dengue virus (DENV) infection and assessed their levels in acute-phase plasma of 109 dengue patients. We show that while both sTLR2 and sCD14 are released by PBMCs in response to DENV infection in vitro, their co-circulation in an acute phase of the disease is not always apparent. In fact, sTLR2 was found only in 20% of patients irrespective of disease status. In contrast, sCD14 levels were detected in all patients and were significantly elevated in DF patients when compared to DHF patients and age-matched healthy donors. Altogether, our results suggest that sCD14 may help in identifying patients at risk of severe dengue at hospital admittance.http://www.sciencedirect.com/science/article/pii/S2405844023044730Dengue virusPBMCssTLR2sCD14Biomarkers
spellingShingle Vinit Upasani
Bram M. ter Ellen
Sotheary Sann
Sokchea Lay
Sothy Heng
Denis Laurent
Sowath Ly
Veasna Duong
Philippe Dussart
Jolanda M. Smit
Tineke Cantaert
Izabela A. Rodenhuis-Zybert
Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection
Heliyon
Dengue virus
PBMCs
sTLR2
sCD14
Biomarkers
title Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection
title_full Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection
title_fullStr Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection
title_full_unstemmed Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection
title_short Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection
title_sort characterization of soluble tlr2 and cd14 levels during acute dengue virus infection
topic Dengue virus
PBMCs
sTLR2
sCD14
Biomarkers
url http://www.sciencedirect.com/science/article/pii/S2405844023044730
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