Th1-polarized, dengue virus-activated human mast cells induce endothelial transcriptional activation and permeability

Ayesa Syenina, Wilfried A. A. Saron, Cyril J. Jagaraj, Siham Bibi, Michel Arock, Duane J. Gubler, Abhay P. S. Rathore, Soman N. Abraham, Ashley L. St. John*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
1 Downloads (Pure)

Abstract

Dengue virus (DENV), an arbovirus, strongly activates mast cells (MCs), which are key immune cells for pathogen immune surveillance. In animal models, MCs promote clearance of local peripheral DENV infections but, conversely, also promote pathological vascular leakage when widely activated during systemic DENV infection. Since DENV is a human pathogen, we sought to ascertain whether a similar phenomenon could occur in humans by characterizing the products released by human MCs (huMCs) upon direct (antibody-independent) DENV exposure, using the phenotypically mature huMC line, ROSA. DENV did not productively infect huMCs but prompted huMC release of proteases and eicosanoids and induced a Th1-polarized transcriptional profile. In co-culture and trans-well systems, huMC products activated human microvascular endothelial cells, involving transcription of vasoactive mediators and increased monolayer permeability. This permeability was blocked by MC-stabilizing drugs, or limited by drugs targeting certain MC products. Thus, MC stabilizers are a viable strategy to limit MC-promoted vascular leakage during DENV infection in humans.

Original languageEnglish
Article number1379
Pages (from-to)1-15
Number of pages15
JournalViruses
Volume12
Issue number12
DOIs
Publication statusPublished - 2 Dec 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Chymase
  • Dengue
  • Endothelial permeability
  • Human
  • Mast cell

Fingerprint

Dive into the research topics of 'Th1-polarized, dengue virus-activated human mast cells induce endothelial transcriptional activation and permeability'. Together they form a unique fingerprint.

Cite this