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Group 2 innate lymphoid cells (ILC2) are type-2 cytokine-producing cells that are activated by epithelial cytokines and mast cell-derived lipid mediators. Through ex vivo RNAseq analysis, we observed that ILC2 are activated during acute dengue viral infection, and show an impaired type I-IFN signature in severe disease. We observed that circulating ILC2 are permissive for dengue virus infection in vivo\u00a0and in vitro, particularly when activated through prostaglandin D<jats:sub>2<\/jats:sub>(PGD<jats:sub>2<\/jats:sub>). ILC2 underwent productive dengue virus infection, which was inhibited through CRTH2 antagonism. Furthermore, exogenous IFN-\u03b2 induced expression of type I-IFN responsive anti-viral genes by ILC2. PGD<jats:sub>2<\/jats:sub>downregulated type I-IFN responsive gene and protein expression; and urinary prostaglandin D<jats:sub>2<\/jats:sub>metabolite levels were elevated in severe dengue. Moreover, supernatants from activated ILC2 enhanced monocyte infection in a GM-CSF and mannan-dependent manner. Our results indicate that dengue virus co-opts an innate type 2 environment to escape early type I-IFN control and facilitate viral dissemination. PGD<jats:sub>2<\/jats:sub>downregulates type I-IFN induced anti-viral responses in ILC2. CRTH2 antagonism may be a therapeutic strategy for dengue-associated disease.<\/jats:p>","DOI":"10.1038\/s42003-022-03682-5","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T15:02:19Z","timestamp":1658502139000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Dengue virus co-opts innate type 2 pathways to escape early control of viral replication"],"prefix":"10.1038","volume":"5","author":[{"given":"Chathuranga L.","family":"Fonseka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1127-6446","authenticated-orcid":false,"given":"Clare S.","family":"Hardman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongmin.","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randeep","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9182-4253","authenticated-orcid":false,"given":"Janina","family":"Nahler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahe","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-0638","authenticated-orcid":false,"given":"Yi-Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achala","family":"Kamaladasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tehani","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Salimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicki","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-0449","authenticated-orcid":false,"given":"Gathsaurie N.","family":"Malavige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-045X","authenticated-orcid":false,"given":"Graham S.","family":"Ogg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"3682_CR1","unstructured":"World Health Organization, Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. 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