Immune responses to Dengue infected microvascular endothelial cells

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 82 - 82.38
• Main Authors: Sekaran, Shamala Devi, Soe, Hui Jen, Raju, Chandramathi Samudi, Manikam, Rishya, Vellasamy, Shalini
• Format: Journal Article
• Language: English
• Published: 01.05.2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.82.38

Abstract Severe dengue is associated with manifestations such as bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from dengue patients. Cytokines and metabolites profiles were also assessed. Our study revealed that dengue NS1 protein was able to induce the loss of barrier function of the microvascular endothelium in a dose dependent manner. However, the level of NS1 did not correlate with the extent of vascular leakage observed in the microvascular endothelium treated with serum samples from patients with dengue virus infection. This implies presence of other host factors that might overshadow the direct effect of NS1 in inducing vascular leakage during dengue virus infection. Most of the cytokines that were highly expressed in dengue patients including CCL2, CCL5, CCL20 and CXCL1 are involved in leukocyte infiltration where the rearrangement of junctional complex proteins such as ICAM-1, which was detected significantly higher in patients with SD, may lead to the disruption of inter-endothelial junctions. Altered lipid metabolism was detected in in patients with DWWS and SD. This might be associated with phospholipid metabolism, which may affect the membrane permeability of cells including the microvascular endothelium. The identification of these altered metabolites could facilitate dengue diagnosis or be used as a potential target for new therapeutic options.