Work

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

Year: 2023

Type: article

Abstract: 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, 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 dengue virus (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. Funding Information: This study has been funded by a Research Grant 2019 from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) to IRZ. TC was funded by the Institute Pasteur International Network and is an HHMI-Wellcome Trust International Research Scholar (208710/Z/17/Z). VU was funded by the Institute Pasteur International Network Calmette and Yersin Ph.D. scholarship and UMCG. Conflict of Interests: The authors have declared that no competing interests exist. Ethical Approval: The clinical study was approved by the National Ethics Committee of Health Research of Cambodia. Written informed consent was obtained from the guardians of participants prior to their inclusion in the study.

Source: Heliyon

DOI: 10.1016/j.heliyon.2023.e17265