{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:39:53Z","timestamp":1778636393113,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81300473"],"award-info":[{"award-number":["81300473"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The structural and functional destruction of the blood-testis barrier (BTB) following uropathogenic<jats:italic>E. coli<\/jats:italic>(UPEC) infection may be a critical component of the pathologic progress of orchitis. Recent findings indicate that the mammalian target of the rapamycin (mTOR)-signaling pathway is implicated in the regulation of BTB assembly and restructuring. To explore the mechanisms underlying BTB damage induced by UPEC infection, we analyzed BTB integrity and the involvement of the mTOR-signaling pathway using<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>UPEC-infection models. We initially confirmed that soluble virulent factors secreted from UPEC trigger a stress response in Sertoli cells and disturb adjacent cell junctions<jats:italic>via<\/jats:italic>down-regulation of junctional proteins, including occludin, zonula occludens-1 (ZO-1), F-actin, connexin-43 (CX-43), \u03b2-catenin, and N-cadherin. The BTB was ultimately disrupted in UPEC-infected rat testes, and blood samples from UPEC-induced orchitis in these animals were positive for anti-sperm antibodies. Furthermore, we herein also demonstrated that mTOR complex 1 (mTORC1) over-activation and mTORC2 suppression contributed to the disturbance in the balance between BTB \u201copening\u201d and \u201cclosing.\u201d More importantly, rapamycin (a specific mTORC1 inhibitor) significantly restored the expression of cell-junction proteins and exerted a protective effect on the BTB during UPEC infection. We further confirmed that short-term treatment with rapamycin did not aggravate spermatogenic degeneration in infected rats. Collectively, this study showed an association between abnormal activation of the mTOR-signaling pathway and BTB impairment during UPEC-induced orchitis, which may provide new insights into a potential treatment strategy for testicular infection.<\/jats:p>","DOI":"10.3389\/fimmu.2021.582858","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T23:42:14Z","timestamp":1613864534000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Uropathogenic Escherichia coli Infection Compromises the Blood-Testis Barrier by Disturbing mTORC1-mTORC2 Balance"],"prefix":"10.3389","volume":"12","author":[{"given":"Yongning","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Tursi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Che","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nianqin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmy009","article-title":"Infectious, inflammatory and \u2018autoimmune\u2019 male factor infertility: how do rodent models inform clinical practice","volume":"24","author":"Fijak","year":"2018","journal-title":"Hum Reprod Update"},{"key":"B2","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1111\/j.1439-0272.2008.00837.x","article-title":"Chronic orchitis: a neglected cause of male infertility","volume":"40","author":"Schuppe","year":"2008","journal-title":"Andrologia"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2008.03.007","article-title":"Origins and virulence mechanisms of uropathogenic Escherichia coli","volume":"85","author":"Wiles","year":"2008","journal-title":"Exp Mol Pathol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.12.005","article-title":"Acute epididymitis revisited: impact of molecular diagnostics on etiology and contemporary guideline recommendations","volume":"68","author":"Pilatz","year":"2015","journal-title":"Eur Urol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-018-3212-z","article-title":"Epididymo-orchitis caused by enteric organisms in men > 35 years old: beyond fluoroquinolones","volume":"37","author":"Ryan","year":"2018","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/5.5.393","article-title":"Mechanisms and effects of male genital tract infection on sperm quality and fertilizing potential: the andrologist\u2019s viewpoint","volume":"5","author":"Comhaire","year":"1999","journal-title":"Hum Reprod Update"},{"key":"B7","article-title":"EAU Guidelines on Sexual and Reproductive Health 2020","volume-title":"European Association of Urology Guidelines 2020 Edition. presented at the EAU Annual Congress Amsterdam 2020. 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