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

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 sy...

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Bibliographic Details
Published in:Viruses 2020-12, Vol.12 (12), p.1379
Main Authors: Syenina, Ayesa, Saron, Wilfried A A, Jagaraj, Cyril J, Bibi, Siham, Arock, Michel, Gubler, Duane J, Rathore, Abhay P S, Abraham, Soman N, St John, Ashley L
Format: Article
Language:English
Subjects:
Animal models
Biomarkers
Capillary Permeability
Cell activation
Cell culture
Cell Degranulation - immunology
chymase
Cytokines
dengue
Dengue - immunology
Dengue - metabolism
Dengue - virology
Dengue fever
Dengue Virus - immunology
Drug delivery
Eicosanoids
Endothelial Cells
endothelial permeability
Endothelium, Vascular - immunology
Endothelium, Vascular - metabolism
Fluorescent Antibody Technique
Gene Expression Profiling
Histocytochemistry
Host-Pathogen Interactions - immunology
human
Human health and pathology
Humans
Immune clearance
Immunosuppressive agents
Immunosurveillance
Life Sciences
Lymphocyte Activation
Lymphocytes T
Macrophages - immunology
Macrophages - metabolism
mast cell
Mast cells
Mast Cells - cytology
Mast Cells - physiology
Membrane permeability
Microvasculature
Pathogens
Permeability
Th1 Cells - physiology
Transcription activation
Transcriptional Activation
Vasoactive agents
Viral infections
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Summary: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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v12121379