{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:26:26Z","timestamp":1790393186179,"version":"4.1.0"},"reference-count":43,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T00:00:00Z","timestamp":1426636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T00:00:00Z","timestamp":1426636800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T00:00:00Z","timestamp":1426636800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council (NMRC)","doi-asserted-by":"publisher","award":["1054\/2011"],"award-info":[{"award-number":["1054\/2011"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Duke-NUS Graduate Medical School","award":["Start-up Funding"],"award-info":[{"award-number":["Start-up Funding"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Dengue virus (DENV) is the most significant human arboviral pathogen and causes \u223c400 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 (&lt;xref ref-type=\"bibr\" rid=\"bib36\"&gt;St John et al., 2013b&lt;\/xref&gt;). 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 Fc\u03b3R-mediated enhanced degranulation responses by MCs. Antibody-dependent mast cell activation constitutes a novel mechanism to explain enhanced vascular leakage during secondary DENV infection.<\/jats:p>","DOI":"10.7554\/elife.05291","type":"journal-article","created":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T10:57:55Z","timestamp":1426589875000},"source":"Crossref","is-referenced-by-count":74,"title":["Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fc\u03b3 receptors"],"prefix":"10.7554","volume":"4","author":[{"given":"Ayesa","family":"Syenina","sequence":"first","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril J","family":"Jagaraj","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti AB","family":"Aman","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Sridharan","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley L","family":"St John","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore"},{"name":"Department of Pathology, Duke University Medical Center, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2015,3,18]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/nri2782","article-title":"Mast cell-orchestrated immunity to pathogens","volume":"10","author":"Abraham","year":"2010","journal-title":"Nature Reviews Immunology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1093\/infdis\/jit436","article-title":"A shorter time interval between first and second dengue infections is associated with protection from clinical illness in a school-based cohort in Thailand","volume":"209","author":"Anderson","year":"2014","journal-title":"The Journal of Infectious Diseases"},{"key":"bib3","first-page":"25","article-title":"Circulating levels of tumour necrosis factor-alpha & interferon-gamma in patients with dengue & dengue haemorrhagic fever during an outbreak","volume":"123","author":"Chakravarti","year":"2006","journal-title":"The Indian Journal of Medical Research"},{"key":"bib4","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.4049\/jimmunol.149.4.1365","article-title":"Murine recombinant Fc gamma RIII, but not Fc gamma RII, trigger serotonin release in rat basophilic leukemia cells","volume":"149","author":"Da\u00ebron","year":"1992","journal-title":"Journal of Immunology"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1126\/science.1185181","article-title":"Cross-reacting antibodies enhance dengue virus infection in humans","volume":"328","author":"Dejnirattisai","year":"2010","journal-title":"Science"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"9422","DOI":"10.1073\/pnas.0703498104","article-title":"Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention","volume":"104","author":"Goncalvez","year":"2007","journal-title":"Proceedings of the National Academy of Sciences of USA"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1086\/528805","article-title":"Dengue and dengue hemorrhagic fever among adults: clinical outcomes related to viremia, serotypes, and antibody response","volume":"197","author":"Guilarde","year":"2008","journal-title":"The Journal of Infectious Diseases"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1126\/science.3277268","article-title":"Pathogenesis of dengue: challenges to molecular biology","volume":"239","author":"Halstead","year":"1988","journal-title":"Science"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1016\/S0140-6736(07)61687-0","article-title":"Dengue","volume":"370","author":"Halstead","year":"2007","journal-title":"Lancet"},{"key":"bib11","first-page":"24","article-title":"Immunological enhancement of dengue virus replication","volume":"243","author":"Halstead","year":"1973","journal-title":"Nature"},{"key":"bib10","first-page":"311","article-title":"Observations related to pathogenesis of dengue hemorrhagic fever. 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