{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:20:03Z","timestamp":1790817603382,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010884","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000}}],"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2018-05209"],"award-info":[{"award-number":["2018-05209"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2018-522661"],"award-info":[{"award-number":["2018-522661"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Schistosoma mansoni<\/jats:italic>employs immune evasion and immunosuppression to overcome immune responses mounted by its snail and human hosts. Myriad immunomodulating factors underlie this process, some of which are proteases. Here, we demonstrate that one protease, an invadolysin we have termed SmCI-1, is released from the acetabular glands of<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>cercaria and is involved in creating an immunological milieu favorable for survival of the parasite. The presence of SmCI-1 in the cercarial stage of<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>is released during transformation into the schistosomula. SmCI-1 functions as a metalloprotease with the capacity to cleave collagen type IV, gelatin and fibrinogen. Additionally, complement component C3b is cleaved by this protease, resulting in inhibition of the classical and alternative complement pathways. Using SmCI-1 knockdown cercariae, we demonstrate that SmCI-1 protects schistosomula from complement-mediated lysis in human plasma. We also assess the effect of SmCI-1 on cytokine release from human peripheral blood mononuclear cells, providing compelling evidence that SmCI-1 promotes an anti-inflammatory microenvironment by enhancing production of IL-10 and suppressing the production of inflammatory cytokines like IL-1B and IL-12p70 and those involved in eosinophil recruitment and activation, like Eotaxin-1 and IL-5. Finally, we utilize the SmCI-1 knockdown cercaria in a mouse model of infection, revealing a role for SmCI-1 in<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>survival.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010884","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T19:38:47Z","timestamp":1675366727000},"page":"e1010884","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["A cercarial invadolysin interferes with the host immune response and facilitates infection establishment of Schistosoma mansoni"],"prefix":"10.1371","volume":"19","author":[{"given":"Jacob R.","family":"Hambrook","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-5012","authenticated-orcid":true,"given":"Patrick C.","family":"Hanington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"issue":"45","key":"ppat.1010884.ref001","first-page":"445","author":"World Health Organization","year":"2018","journal-title":"The Weekly Epidemiological Record (WER) WHO"},{"issue":"11","key":"ppat.1010884.ref002","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.pt.2017.07.006","article-title":"Schistosomiasis from a Snail\u2019s Perspective","volume":"33","author":"EA Pila","year":"2017","journal-title":"Advances in Snail Immunity Trends Parasitol"},{"issue":"1","key":"ppat.1010884.ref003","first-page":"3820","article-title":"Immune Evasion Strategies of Schistosomes","volume":"11","author":"JR Hambrook","year":"2021","journal-title":"Front Immunol"},{"key":"ppat.1010884.ref004","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.3389\/fimmu.2020.01018","article-title":"Behind Enemy Lines: Immunomodulatory Armamentarium of the Schistosome Parasite","volume":"11","author":"JMM Angeles","year":"2020","journal-title":"Frontiers in Immunology. 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