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

Publication ,  Journal Article
Syenina, A; Saron, WAA; Jagaraj, CJ; Bibi, S; Arock, M; Gubler, DJ; Rathore, APS; Abraham, SN; St John, AL
Published in: Viruses
December 2, 2020

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.

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Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

December 2, 2020

Volume

12

Issue

12

Location

Switzerland

Related Subject Headings

  • Transcriptional Activation
  • Th1 Cells
  • Mast Cells
  • Macrophages
  • Lymphocyte Activation
  • Humans
  • Host-Pathogen Interactions
  • Histocytochemistry
  • Gene Expression Profiling
  • Fluorescent Antibody Technique
 

Citation

APA
Chicago
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MLA
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Syenina, A., Saron, W. A. A., Jagaraj, C. J., Bibi, S., Arock, M., Gubler, D. J., … St John, A. L. (2020). Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability. Viruses, 12(12). https://doi.org/10.3390/v12121379
Syenina, Ayesa, Wilfried A. A. Saron, Cyril J. Jagaraj, Siham Bibi, Michel Arock, Duane J. Gubler, Abhay P. S. Rathore, Soman N. Abraham, and Ashley L. St John. “Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability.Viruses 12, no. 12 (December 2, 2020). https://doi.org/10.3390/v12121379.
Syenina A, Saron WAA, Jagaraj CJ, Bibi S, Arock M, Gubler DJ, et al. Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability. Viruses. 2020 Dec 2;12(12).
Syenina, Ayesa, et al. “Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability.Viruses, vol. 12, no. 12, Dec. 2020. Pubmed, doi:10.3390/v12121379.
Syenina A, Saron WAA, Jagaraj CJ, Bibi S, Arock M, Gubler DJ, Rathore APS, Abraham SN, St John AL. Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability. Viruses. 2020 Dec 2;12(12).

Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

December 2, 2020

Volume

12

Issue

12

Location

Switzerland

Related Subject Headings

  • Transcriptional Activation
  • Th1 Cells
  • Mast Cells
  • Macrophages
  • Lymphocyte Activation
  • Humans
  • Host-Pathogen Interactions
  • Histocytochemistry
  • Gene Expression Profiling
  • Fluorescent Antibody Technique