Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection
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
Affiliations
Vinit Upasani
Immunology 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, Netherlands
Bram M. ter Ellen
Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, Netherlands
Sotheary Sann
Immunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
Sokchea Lay
Immunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
Sothy Heng
Kantha Bopha Children Hospital, Phnom Penh, Cambodia
Denis Laurent
Kantha Bopha Children Hospital, Phnom Penh, Cambodia
Sowath Ly
Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
Veasna Duong
Virology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
Philippe Dussart
Virology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia
Jolanda M. Smit
Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, Netherlands
Tineke Cantaert
Immunology Unit, Institut Pasteur du Cambodge, Pasteur Network, Phnom Penh, Cambodia; Corresponding author.
Izabela A. Rodenhuis-Zybert
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.
