{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:42:14Z","timestamp":1785152534003,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Candida albican<\/jats:italic>s is the leading cause of candidemia or other invasive candidiasis. Gastrointestinal colonization has been considered as the primary source of candidemia. However, few established mouse models that mimic this infection route are available. In the present study, we established a mouse model of disseminated candidiasis developed through the translocation of<jats:italic>Candida<\/jats:italic>from the gut. In this study, we developed a novel<jats:italic>C. albicans<\/jats:italic>GI colonization and dissemination animal model by using severe combined immunodeficient Rag2<jats:sup>\u2013\/\u2013<\/jats:sup>IL2\u03b3c<jats:sup>\u2013\/\u2013<\/jats:sup>(Rag2\u03b3c) mice, which lack functional T, B, NK cells, and IL2\u03b3c-dependent signaling. Rag2\u03b3c mice were highly susceptible to<jats:italic>C. albicans<\/jats:italic>gastrointestinal infection even in the presence of the gut microbiota. Within 4 weeks post infection, Rag2\u03b3c mice showed dose-dependent weight loss and disseminated candidiasis in more than 58% (7\/12) of moribund mice. Histological analysis demonstrated abundant hyphae penetrating the mucosa, with significant neutrophilic infiltration in mice infected with wild-type<jats:italic>C. albicans<\/jats:italic>but not a filamentation-defective mutant. In moribund Rag2\u03b3c mice, the necrotic lesions and disrupted epithelial cells were associated with<jats:italic>C. albicans<\/jats:italic>hyphae. Notably, removal of the gut microbiota by antibiotics exacerbated the severity of fungal infection in Rag2\u03b3c mice, as demonstrated by elevated fungal burdens and accelerated weight loss and death. Furthermore, higher fungal burden and IL-1\u03b2 expression were prominently noted in the stomach of Rag2\u03b3c mice. In fact, a significant increase in circulating proinflammatory cytokines, including IL-6, TNF-\u03b1, and IL-10, indicative of a septic response, was evident in infected Rag2\u03b3c mice. Additionally, Rag2\u03b3c mice exhibited significantly lower levels of IL-22 but not IFN-\u03b3 or IL-17A than wild-type B6 mice, suggesting that IL-22 plays a role in<jats:italic>C. albicans<\/jats:italic>gastrointestinal infection. Collectively, our analysis of the Rag2\u03b3c mouse model revealed features of<jats:italic>C. albicans<\/jats:italic>gastrointestinal colonization and dissemination without the interference from antibiotics or chemotherapeutic agents, thus offering a new investigative tool for delineating the pathogenesis of<jats:italic>C. albicans<\/jats:italic>and its cross-talk with the gut microbiota.<\/jats:p>","DOI":"10.3389\/fmicb.2020.619878","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T04:38:51Z","timestamp":1610080731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Candida albicans Colonizes and Disseminates to the Gastrointestinal Tract in the Presence of the Microbiota in a Severe Combined Immunodeficient Mouse Model"],"prefix":"10.3389","volume":"11","author":[{"given":"Chien-Hsiung","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Jung","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Ying","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ju","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Wei","family":"Hsueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di-Wei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Han","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sze-Hsien","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Chun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e915","DOI":"10.1128\/mBio.00915-18","article-title":"Candida albicans-Induced epithelial damage mediates translocation through intestinal barriers.","volume":"9","author":"Allert","year":"2018","journal-title":"MBio"},{"key":"B2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/mmy.39.3.261.268","article-title":"Oroesophageal candidiasis is lethal for transgenic mice with combined natural killer and T-cell defects.","volume":"39","author":"Balish","year":"2001","journal-title":"Med. 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