Serum from dengue virus-infected patients with and without plasma leakage differentially affects endothelial cells barrier function in vitro

Author(s)

Gomes de Sousa Cardozo, Francielle Tramontini ; Baimukanova, Gyulnar ; Lanteri, Marion Christine ; Keating, Sheila Marie ; Ferreira, Frederico Moraes ; Heitman, John ; Pannuti, Claudio Sergio ; Pati, Shibani ; Romano, Camila Malta ; Sabino, Ester Cerdeira

• Document type: Journal article
• Source: PLoS One; v. 12, n. 6 JUN 6 2017.
• Web of Science Citations: 8

Abstract

Background Although most of cases of dengue infections are asymptomatic or mild symptomatic some individuals present warning signs progressing to severe dengue in which plasma leakage is a hallmark. Methodology/Principal findings The present study used Electric Cell-substrate Impedance Sensing (ECIS (R)) which allows for electrical monitoring of cellular barrier function measuring changes in Transendothelial Electric Resistance (TEER) to investigate the parameters associated with dengue induced leakage. Three groups of individuals were tested: dengue-positives with plasma leakage (leakage), dengue-positives without plasma leakage (no leakage), and dengue-negatives (control). Data show that TEER values of human umbilical vein endothelial cells (HUVECs) was significantly lower after incubation with serum from subjects of the leakage group in comparison to the no leakage or control groups. The serum levels of CXCL1, EGF, eotaxin, IFN-gamma, sCD40L, and platelets were significantly decreased in the leakage group, while IL-10, IL-6, and IP-10 levels were significantly increased. We also found a strong correlation between TEER values and augmented levels of IP-10, GM-CSF, IL-1 alpha, and IL-8, as well as decreased levels of CXCL1 and platelets. Conclusions/Significance The present work shows that the magnitude of the immune response contributes to the adverse plasma leakage outcomes in patients and that serum components are important mediators of changes in endothelial homeostasis during dengue infections. In particular, the increased levels of IP-10 and the decreased levels of CXCL1 and platelets seem to play a significant role in the disruption of vascular endothelium associated with leakage outcomes after DENV infection. These findings may have important implications for both diagnostic and therapeutic approaches to predict and mitigate vascular permeabilization in those experiencing the most severe clinical disease outcomes after dengue infection. (AU)

• FAPESP's process: 13/01690-0 - Establishment of an in vitro model of vascular permeability evaluation to study the hemorrhagic dengue fever pathogenesis and screening of compounds with therapeutic potential
• Grantee: Ester Cerdeira Sabino
• Support type: Regular Research Grants
• FAPESP's process: 13/01702-9 - Evaluation of endothelial permeability to study dengue pathogenesis and screen compounds with therapeutic potential
• Grantee: Francielle Tramontini Gomes de Sousa
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 12/15381-7 - Characterization of adaptive mutations in dengue virus serotype 2 (DENV2) cultured in different systems using high-throughput sequencing
• Grantee: Camila Malta Romano
• Support type: Regular Research Grants