{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:31Z","timestamp":1787022211845,"version":"build-2736575974"},"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI148656"],"award-info":[{"award-number":["R01 AI148656"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI018919"],"award-info":[{"award-number":["R01 AI018919"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM108563-06"],"award-info":[{"award-number":["T32 GM108563-06"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM154124-01"],"award-info":[{"award-number":["T32 GM154124-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Infection with the helminth\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    can cause exacerbated morbidity and mortality via a pathogenic host CD4 T cell-mediated immune response directed against parasite egg antigens, with T helper (Th) 17 cells playing a major role in the development of severe granulomatous hepatic immunopathology. The role of inflammasomes in intensifying disease has been reported; however, neither the types of caspases and inflammasomes involved, nor their impact on the Th17 response are known. Here we show that enhanced egg-induced IL-1\u03b2 secretion and pyroptotic cell death required both caspase-1 and caspase-8 as well as NLRP3 and AIM2 inflammasome activation. Schistosome genomic DNA activated AIM2, whereas reactive oxygen species, potassium efflux and cathepsin B, were the major activators of NLRP3. NLRP3 and AIM2 deficiency led to a significant reduction in pathogenic Th17 responses, suggesting their crucial and non-redundant role in promoting inflammation. Additionally, we show that NLRP3- and AIM2-induced IL-1\u03b2 suppressed IL-4 and protective Type I IFN (IFN-I) production, which further enhanced inflammation. IFN-I signaling also curbed inflammasome- mediated IL-1\u03b2 production suggesting that these two antagonistic pathways shape the severity of disease. Lastly, Gasdermin D (Gsdmd) deficiency resulted in a marked decrease in egg-induced granulomatous inflammation. Our findings establish NLRP3\/AIM2-Gsdmd axis as a central inducer of pathogenic Th17 responses which is counteracted by IFN-I pathway in schistosomiasis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012108","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T13:43:12Z","timestamp":1742305392000},"page":"e1012108","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["NLRP3 and AIM2 inflammasomes exacerbate the pathogenic Th17 cell response to eggs of the helminth Schistosoma mansoni"],"prefix":"10.1371","volume":"21","author":[{"given":"Madhusoodhanan","family":"Suresh Kumar Meena Kumari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan S.","family":"Nitchman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santoshi","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaile","family":"Jump","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoelkys","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Shecter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel J.","family":"Stadecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0159-474X","authenticated-orcid":true,"given":"Parisa","family":"Kalantari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"issue":"11","key":"ppat.1012108.ref001","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1016\/S1473-3099(22)00221-3","article-title":"Review of 2022 WHO guidelines on the control and elimination of schistosomiasis","volume":"22","author":"NC Lo","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"ppat.1012108.ref002","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/eji.1830270518","article-title":"Expression of class II, but not class I, major histocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni","volume":"27","author":"HJ Hernandez","year":"1997","journal-title":"Eur J Immunol"},{"issue":"4","key":"ppat.1012108.ref003","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/eji.1830250404","article-title":"T cells expressing the gamma delta T cell receptor are not required for egg granuloma formation in schistosomiasis","volume":"25","author":"J Iacomini","year":"1995","journal-title":"Eur J Immunol"},{"issue":"2","key":"ppat.1012108.ref004","doi-asserted-by":"crossref","first-page":"594","DOI":"10.4049\/jimmunol.118.2.594","article-title":"Schistosomiasis in the congenitally athymic (nude) mouse. 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Thymic dependency of eosinophilia, granuloma formation, and host morbidity","volume":"118","author":"SM Phillips","year":"1977","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1012108.ref005","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23042255","article-title":"Vaccines for Human Schistosomiasis: Recent Progress, New Developments and Future Prospects","volume":"23","author":"AJ Molehin","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"47","key":"ppat.1012108.ref006","doi-asserted-by":"crossref","first-page":"20459","DOI":"10.1073\/pnas.1010337107","article-title":"Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses","volume":"107","author":"M Ritter","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1012108.ref007","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/j.celrep.2018.01.001","article-title":"CD209a Synergizes with Dectin-2 and Mincle to Drive 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