Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fcγ receptors

ELife
Ayesa SyeninaAshley L St John

Abstract

Dengue virus (DENV) is the most significant human arboviral pathogen and causes ∼400 million infections in humans each year. In previous work, we observed that mast cells (MC) mediate vascular leakage during DENV infection in mice and that levels of MC activation are correlated with disease severity in human DENV patients (St John et al., 2013b). A major risk factor for developing severe dengue is secondary infection with a heterologous serotype. The dominant theory explaining increased severity during secondary DENV infection is that cross-reactive but non-neutralizing antibodies promote uptake of virus and allow enhanced replication. Here, we define another mechanism, dependent on FcγR-mediated enhanced degranulation responses by MCs. Antibody-dependent mast cell activation constitutes a novel mechanism to explain enhanced vascular leakage during secondary DENV infection.

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Citations

Jun 5, 2015·Frontiers in Immunology·Amy C GrahamJoshua J Obar
May 10, 2017·DNA and Cell Biology·Berlin Londono-RenteriaTonya M Colpitts
Apr 25, 2017·Immunology·Gathsaurie Neelika Malavige, Graham S Ogg
Feb 12, 2019·Nature Communications·Justin T HsiehAshley L St John
Mar 3, 2018·Scientific Reports·Gathsaurie Neelika MalavigeGraham S Ogg
Jul 3, 2019·The Journal of Clinical Investigation·Abhay Ps RathoreAshley L St John
Sep 5, 2019·International Journal of Molecular Sciences·Jean S MarshallEdwin Leong
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Oct 3, 2017·The Journal of Infectious Diseases·Hasitha TisseraAshley L St John
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Aug 24, 2018·Open Biology·Abhay P S Rathore, Ashley L St John
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Mar 17, 2020·Frontiers in Immunology·Abhay P S Rathore, Ashley L St John
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May 1, 2021·International Journal of Molecular Sciences·Martin VossAnne Dudeck
Jun 26, 2021·Frontiers in Immunology·Abhay P S RathoreAshley L St John
Jul 2, 2021·Frontiers in Immunology·Yana HacklerMelba Muñoz
Oct 27, 2021·Virulence·Sophie Wilhelmina van LeurSumana Sanyal

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Methods Mentioned

BETA
flow cytometry
confocal
lavage
ELISA
biopsy

Software Mentioned

Prism
Excel

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