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However, the regulatory mechanisms underlying antifungal immunity remain elusive and require further investigation. The E3 ligase Trim26 belongs to the tripartite motif (Trim) protein family, which is involved in various biological processes, including cell proliferation, antiviral innate immunity, and inflammatory responses. Herein, we report that Trim26 exerts protective antifungal immune functions after fungal infection. <jats:italic>Trim26<\/jats:italic>-deficient mice are more susceptible to fungemia than their wild-type counterparts. Mechanistically, Trim26 restricts inflammatory neutrophils infiltration and limits proinflammatory cytokine production, which can attenuate kidney fungal load and renal damage during <jats:italic>Candida<\/jats:italic> infection. Trim26-deficient neutrophils showed higher proinflammatory cytokine expression and impaired fungicidal activity. We further demonstrated that excessive neutrophils infiltration in the kidney was because of the increased production of chemokines CXCL1 and CXCL2, which are mainly synthesized in the macrophages or dendritic cells of <jats:italic>Trim26<\/jats:italic>-deficient mice after <jats:italic>Candida albicans<\/jats:italic> infections. Together, our study findings unraveled the vital role of Trim26 in regulating antifungal immunity through the regulation of inflammatory neutrophils infiltration and proinflammatory cytokine and chemokine expression during candidiasis.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011902","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T20:13:52Z","timestamp":1704226432000},"page":"e1011902","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["TRIM26 alleviates fatal immunopathology by regulating inflammatory neutrophil infiltration during Candida infection"],"prefix":"10.1371","volume":"20","author":[{"given":"Guimin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9365-4497","authenticated-orcid":true,"given":"Chengjiang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,2]]},"reference":[{"issue":"9","key":"ppat.1011902.ref001","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1086\/496922","article-title":"The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis","volume":"41","author":"TE Zaoutis","year":"2005","journal-title":"Clin Infect Dis"},{"issue":"2","key":"ppat.1011902.ref002","doi-asserted-by":"crossref","first-page":"e01229","DOI":"10.1128\/AAC.01229-16","article-title":"Echinocandin Resistance in Candida Species Isolates from Liver Transplant Recipients","volume":"61","author":"G Prigent","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"ppat.1011902.ref003","first-page":"11","article-title":"Emerging Threats in Antifungal-Resistant Fungal Pathogens","volume":"3","author":"D. 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Akcay","year":"2009","journal-title":"Mediators Inflamm"},{"issue":"13","key":"ppat.1011902.ref034","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1089\/ars.2020.8030","article-title":"The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and","volume":"32","author":"MJ Davies","year":"2020","journal-title":"Disease Antioxid Redox Signal"},{"issue":"2","key":"ppat.1011902.ref035","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.chom.2020.12.016","article-title":"Induction of alarmin S100A8\/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19","volume":"29","author":"Q Guo","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ppat.1011902.ref036","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.mib.2020.10.003","article-title":"The first line of defense: effector pathways of anti-fungal innate immunity","volume":"58","author":"RA Ward","year":"2020","journal-title":"Curr Opin 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