title: Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fcγ receptors.
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.
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore.
authors.forename: Ayesa
authors.initials: A
authors.lastname: Syenina
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore.
authors.forename: Cyril J
authors.initials: CJ
authors.lastname: Jagaraj
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore.
authors.forename: Siti A B
authors.initials: SA
authors.lastname: Aman
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Sridharan
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: St John
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000502:physiology / Q000821:virology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG
keywords: Fc receptor; antibodies; dengue virus; immunology; infectious disease; mast cell; microbiology; mouse; vascular leakage