{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:46:09Z","timestamp":1785224769616,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011816","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802025"],"award-info":[{"award-number":["81802025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Henan Province Science and Technology key project","award":["212102310146"],"award-info":[{"award-number":["212102310146"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172300"],"award-info":[{"award-number":["82172300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Cathepsin L, a lysosomal enzyme, participates in diverse physiological processes. Recombinant <jats:italic>Trichinella spiralis<\/jats:italic> cathepsin L domains (rTsCatL2) exhibited natural cysteine protease activity and hydrolyzed host immunoglobulin and extracellular matrix proteins in vitro, but its functions in larval invasion are unknown. The aim of this study was to explore its functions in <jats:italic>T<\/jats:italic>. <jats:italic>spiralis<\/jats:italic> invasion of the host\u2019s intestinal epithelial cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/principal findings<\/jats:title>\n<jats:p>RNAi significantly suppressed the expression of TsCatL mRNA and protein with TsCatL specific siRNA-302. <jats:italic>T<\/jats:italic>. <jats:italic>spiralis<\/jats:italic> larval invasion of Caco-2 cells was reduced by 39.87% and 38.36%, respectively, when anti-TsCatL2 serum and siRNA-302 were used. Mice challenged with siRNA-302-treated muscle larvae (ML) exhibited a substantial reduction in intestinal infective larvae, adult worm, and ML burden compared to the PBS group, with reductions of 44.37%, 47.57%, and 57.06%, respectively. The development and fecundity of the females from the mice infected with siRNA-302-treated ML was significantly inhibited. After incubation of rTsCatL2 with Caco-2 cells, immunofluorescence test showed that the rTsCatL2 gradually entered into the cells, altered the localization of cellular tight junction proteins (claudin 1, occludin and zo-1), adhesion junction protein (e-cadherin) and extracellular matrix protein (laminin), and intercellular junctions were lost. Western blot showed a 58.65% reduction in claudin 1 expression in Caco-2 cells treated with rTsCatL2. Co-IP showed that rTsCatL2 interacted with laminin and collagen I but not with claudin 1, e-cadherin, occludin and fibronectin in Caco-2 cells. Moreover, rTsCatL2 disrupted the intestinal epithelial barrier by inducing cellular autophagy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>rTsCatL2 disrupts the intestinal epithelial barrier and facilitates <jats:italic>T<\/jats:italic>. <jats:italic>spiralis<\/jats:italic> larval invasion.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011816","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T18:30:03Z","timestamp":1701714603000},"page":"e0011816","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Trichinella spiralis cathepsin L damages the tight junctions of intestinal epithelial cells and mediates larval invasion"],"prefix":"10.1371","volume":"17","author":[{"given":"Ruo Dan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang 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