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Inflammasome activation has recently been implicated in the pathogenesis of liver disease. However, the role of inflammasome activation in schistosomiasis-associated liver fibrosis (SSLF) has not been extensively studied. In this study, it is demonstrated that the NLRP3 inflammasome is markedly activated in mouse HSCs both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> during <jats:italic>S. japonicum<\/jats:italic> infection. Furthermore, it is demonstrated that inhibition of NLRP3 inflammasome significantly alleviates the liver inflammation and collagen deposition that are induced by infection with <jats:italic>S. japonicum<\/jats:italic>. The mechanism of SEA-induced NLRP3 inflammasome activation is studied in isolated, cultured mouse HSCs and it is shown that SEA-induced NLRP3 inflammasome activation in HSCs is dependent upon the activities of spleen tyrosine kinase (Syk), an enzyme usually associated with a pathogen recognition receptor for fungal pathogens. Moreover, it is demonstrated that Dectin-1 and JNK signaling are also involved in SEA-induced NLRP3 inflammasome activation in HSCs. These data shed new light on the mechanisms of NLRP3 inflammasome activation during an infection with <jats:italic>S. japonicum<\/jats:italic>, and further characterize its role in schistosomiasis-associated liver fibrosis (SSLF).<\/jats:p>","DOI":"10.1038\/s41598-017-08689-1","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T15:52:45Z","timestamp":1502207565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["NLRP3 inflammasome activation results in liver inflammation and fibrosis in mice infected with Schistosoma japonicum in a Syk-dependent manner"],"prefix":"10.1038","volume":"7","author":[{"given":"Ya-Qi","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Ping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang-Xian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"8689_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002490","volume":"8","author":"KC Fairfax","year":"2012","unstructured":"Fairfax, K. 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