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

Ayesa Syenina, Cyril J. Jagaraj, Siti A.B. Aman, Aishwarya Sridharan, Ashley L.St John*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)
1 Downloads (Pure)

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 nonneutralizing 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.

Original languageEnglish
Article numbere05291
Pages (from-to)1-16
Number of pages16
JournaleLife
Volume2015
Issue number4
DOIs
Publication statusPublished - 18 Mar 2015
Externally publishedYes

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