{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:27:50Z","timestamp":1781886470548,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016017","name":"Duke-NUS Medical School","doi-asserted-by":"publisher","award":["Duke\/Duke-NUS\/RECA\/2012\/0003"],"award-info":[{"award-number":["Duke\/Duke-NUS\/RECA\/2012\/0003"]}],"id":[{"id":"10.13039\/100016017","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Medical Research Council, Singapore","award":["NMRC\/CBRG\/0084\/2015"],"award-info":[{"award-number":["NMRC\/CBRG\/0084\/2015"]}]},{"name":"Embassy of France in Singapore","award":["Merlion award"],"award-info":[{"award-number":["Merlion award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Dengue virus (DENV), an arbovirus, strongly activates mast cells (MCs), which are key immune cells for pathogen immune surveillance. In animal models, MCs promote clearance of local peripheral DENV infections but, conversely, also promote pathological vascular leakage when widely activated during systemic DENV infection. Since DENV is a human pathogen, we sought to ascertain whether a similar phenomenon could occur in humans by characterizing the products released by human MCs (huMCs) upon direct (antibody-independent) DENV exposure, using the phenotypically mature huMC line, ROSA. DENV did not productively infect huMCs but prompted huMC release of proteases and eicosanoids and induced a Th1-polarized transcriptional profile. In co-culture and trans-well systems, huMC products activated human microvascular endothelial cells, involving transcription of vasoactive mediators and increased monolayer permeability. This permeability was blocked by MC-stabilizing drugs, or limited by drugs targeting certain MC products. Thus, MC stabilizers are a viable strategy to limit MC-promoted vascular leakage during DENV infection in humans.<\/jats:p>","DOI":"10.3390\/v12121379","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T07:49:54Z","timestamp":1606895394000},"page":"1379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability"],"prefix":"10.3390","volume":"12","author":[{"given":"Ayesa","family":"Syenina","sequence":"first","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-5288","authenticated-orcid":false,"given":"Wilfried A. A.","family":"Saron","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, 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 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siham","family":"Bibi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Oncology, LBPA CNRS UMR8113, Ecole Normale Sup\u00e9rieure de Cachan, 94235 Cachan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-4408","authenticated-orcid":false,"given":"Michel","family":"Arock","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Oncology, LBPA CNRS UMR8113, Ecole Normale Sup\u00e9rieure de Cachan, 94235 Cachan, France"},{"name":"Laboratory of Hematology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Pierre et Marie Curie University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duane J.","family":"Gubler","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay P. S.","family":"Rathore","sequence":"additional","affiliation":[{"name":"Pathology Department, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soman N.","family":"Abraham","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore"},{"name":"Pathology Department, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Immunology Department, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Molecular Genetics and Microbiology Departments, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5098-1044","authenticated-orcid":false,"given":"Ashley L.","family":"St. John","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore"},{"name":"Pathology Department, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Department of Microbiology and Immunology, National University of Singapore, Singapore 117545, Singapore"},{"name":"SingHealth Duke-NUS Global Health Institute, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.4049\/jimmunol.1203420","article-title":"Innate Immunity and Its Regulation by Mast Cells","volume":"190","author":"Abraham","year":"2013","journal-title":"J. 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