Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Syenina, A; Saron, WAA; Jagaraj, CJ; Bibi, S; Arock, M; Gubler, DJ; Rathore, APS; Abraham, SN; St John, AL

Published Date

  • December 2, 2020

Published In

Volume / Issue

  • 12 / 12

PubMed ID

  • 33276578

Pubmed Central ID

  • PMC7761533

Electronic International Standard Serial Number (EISSN)

  • 1999-4915

Digital Object Identifier (DOI)

  • 10.3390/v12121379

Language

  • eng

Conference Location

  • Switzerland