Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fcγ receptors
A Syenina, CJ Jagaraj, SAB Aman, A Sridharan… - elife, 2015 - elifesciences.org
elife, 2015•elifesciences.org
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. 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 …
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. 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 …
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 . 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.
DOI: http://dx.doi.org/10.7554/eLife.05291.001
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