{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:42:42Z","timestamp":1783996962976,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFD0502303, 2017YFD0501605"],"award-info":[{"award-number":["2017YFD0502303, 2017YFD0501605"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013058","name":"Jiangsu Provincial Key Research and Development Program","doi-asserted-by":"publisher","award":["BE2020674"],"award-info":[{"award-number":["BE2020674"]}],"id":[{"id":"10.13039\/501100013058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["PAPD"],"award-info":[{"award-number":["PAPD"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>It has been well documented that cytolethal distending toxin (CDT) from <jats:italic>Helicobacter hepaticus<\/jats:italic> (<jats:italic>H. hepaticus<\/jats:italic>), <jats:italic>Campylobacter jejuni<\/jats:italic> (<jats:italic>C. jejuni<\/jats:italic>) and other Gram-negative intestinal pathogens is linked to the inflammatory bowel disease (IBD). However, the mechanisms underlying the progression of <jats:italic>H. hepaticus<\/jats:italic> induced colitis remains unclear. In this study, male B6.129P2-<jats:italic>IL10<jats:sup>tm1Cgn<\/jats:sup><\/jats:italic>\/J mice were infected by <jats:italic>H. hepaticus<\/jats:italic> and \u0394CdtB <jats:italic>H. hepaticus<\/jats:italic> for 6, 12, 18, and 24 weeks. Histopathology, <jats:italic>H. hepaticus<\/jats:italic> colonization levels, expression of inflammatory cytokines, signaling pathways, and content of NO in proximal colon were examined. We found that Cytolethal distending toxin subunit B (CdtB) deletion had no influence on colonization ability of <jats:italic>H. hepaticus<\/jats:italic> in colon of B6.129P2-<jats:italic>IL10<jats:sup>tm1cgn<\/jats:sup><\/jats:italic><jats:sup>\/<\/jats:sup>J mice, and there was no significant difference in abundance of colonic <jats:italic>H. hepaticus<\/jats:italic> over infection duration. <jats:italic>H. hepaticus<\/jats:italic> aggravated rectocele and proximal colonic inflammation, especially at 24 WPI, while \u0394CdtB <jats:italic>H. hepaticus<\/jats:italic> could not cause significant symptom. Furthermore, mRNA levels of <jats:italic>Il-6<\/jats:italic>, <jats:italic>Tnf-\u03b1<\/jats:italic>, <jats:italic>Il-1\u03b2<\/jats:italic>, and <jats:italic>iNOS<\/jats:italic> significantly increased in the proximal colon of <jats:italic>H. hepaticus<\/jats:italic>-infected mice compared to \u0394CdtB <jats:italic>H. hepaticus<\/jats:italic> infected group from 12 WPI to 24 WPI. In addition, the elevated content of NO and activated <jats:italic>Stat3<\/jats:italic> and <jats:italic>Jak2<\/jats:italic> in colon were observed in <jats:italic>H. hepaticus<\/jats:italic> infected mice. These data demonstrated that CdtB promote colitis development in male B6.129P2-<jats:italic>IL10<jats:sup>tm1Cgn<\/jats:sup><\/jats:italic>\/J mice by induction of inflammatory response and activation of <jats:italic>Jak<\/jats:italic>-<jats:italic>Stat<\/jats:italic> signaling pathway.<\/jats:p>","DOI":"10.3389\/fcimb.2021.616218","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T06:15:19Z","timestamp":1615529719000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Helicobacter hepaticus Induce Colitis in Male IL-10\u2212\/\u2212 Mice Dependent by Cytolethal Distending Toxin B and via the Activation of Jak\/Stat Signaling Pathway"],"prefix":"10.3389","volume":"11","author":[{"given":"Liqi","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0185382","DOI":"10.1371\/journal.pone.0185382","article-title":"Intestinal anti-inflammatory effects of goat whey on DNBS-induced colitis in mice","volume":"12","author":"Araujo","year":"2017","journal-title":"PloS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1136\/gut.2005.085373","article-title":"Alterations in intestinal permeability","volume":"55","author":"Arrieta","year":"2006","journal-title":"Gut"},{"key":"B3","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.bbrc.2004.04.089","article-title":"Expression and activity of the cytolethal distending toxin of Helicobacter hepaticus","volume":"318","author":"Avenaud","year":"2004","journal-title":"Biochem. 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