{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:15:13Z","timestamp":1780082113884,"version":"3.54.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009200","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000}}],"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Therapeutic Accelerator Program"},{"name":"New Faculty Pilot Grant\/Medical College of Wisconsin"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R21AI153545-01"],"award-info":[{"award-number":["1R21AI153545-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Control of the neglected tropical disease schistosomiasis relies almost entirely on praziquantel (PZQ) monotherapy. How PZQ clears parasite infections remains poorly understood. Many studies have examined the effects of PZQ on worms cultured<jats:italic>in vitro<\/jats:italic>, observing outcomes such as muscle contraction. However, conditions worms are exposed to<jats:italic>in vivo<\/jats:italic>may vary considerably from<jats:italic>in vitro<\/jats:italic>experiments given the short half-life of PZQ and the importance of host immune system engagement for drug efficacy in animal models. Here, we investigated the effects of<jats:italic>in vivo<\/jats:italic>PZQ exposure on<jats:italic>Schistosoma mansoni<\/jats:italic>. Measurement of pro-apoptotic caspase activation revealed that worm death occurs only after parasites shift from the mesenteric vasculature to the liver, peaking 24 hours after drug treatment. This indicates that PZQ is not directly schistocidal, since PZQ\u2019s half-life is ~2 hours in humans and ~30 minutes in mice, and focuses attention on parasite interactions with the host immune system following the shift of worms to the liver. RNA-Seq of worms harvested from mouse livers following sub-lethal PZQ treatment revealed drug-evoked changes in the expression of putative immunomodulatory and anticoagulant gene products. Several of these gene products localized to the schistosome esophagus and may be secreted into the host circulation. These include several Kunitz-type protease inhibitors, which are also found in the secretomes of other blood feeding animals. These transcriptional changes may reflect mechanisms of parasite immune-evasion in response to chemotherapy, given the role of complement-mediated attack and the host innate\/humoral immune response in parasite elimination. One of these isoforms, SmKI-1, has been shown to exhibit immunomodulatory and anti-coagulant properties. These data provide insight into the effect of<jats:italic>in vivo<\/jats:italic>PZQ exposure on<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>, and the transcriptional response of parasites to the stress of chemotherapy.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009200","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T19:44:31Z","timestamp":1614800671000},"page":"e0009200","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Schistosoma mansoni alter transcription of immunomodulatory gene products following in vivo praziquantel exposure"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0030-1594","authenticated-orcid":true,"given":"Paul","family":"McCusker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0065-7160","authenticated-orcid":true,"given":"Claudia M.","family":"Rohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-972X","authenticated-orcid":true,"given":"John D.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"issue":"1","key":"pntd.0009200.ref001","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/glycob\/cwp140","article-title":"Glycan gimmickry by parasitic helminths: a strategy for modulating the host immune response?","volume":"20","author":"I van Die","year":"2010","journal-title":"Glycobiology"},{"key":"pntd.0009200.ref002","doi-asserted-by":"crossref","first-page":"13434","DOI":"10.1038\/srep13434","article-title":"Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition","volume":"5","author":"C Wu","year":"2015","journal-title":"Sci Rep"},{"key":"pntd.0009200.ref003","first-page":"e47882","article-title":"Schistosomal extracellular vesicle-enclosed miRNAs modulate host T helper cell differentiation","author":"T Meningher","year":"2019","journal-title":"EMBO Rep"},{"issue":"9936","key":"pntd.0009200.ref004","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"DG Colley","year":"2014","journal-title":"Lancet"},{"key":"pntd.0009200.ref005","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/BF00507974","article-title":"A benzodiazepine derivative and praziquantel: effects on musculature of Schistosoma mansoni and Schistosoma japonicum","volume":"304","author":"R Pax","year":"1978","journal-title":"Archives Pharmacol"},{"key":"pntd.0009200.ref006","first-page":"36873","article-title":"Schistosome calcium channel beta subunits. 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