TRIM26 alleviates fatal immunopathology by regulating inflammatory neutrophil infiltration during Candida infection

• DOI: 10.1371/journal.ppat.1011902
• Publication Date: 2024-01-02T20:13:52Z
• Authors: Guimin Zhao; Yanqi Li; Tian Chen; Feng Liu; Yi Zheng; Bingyu Liu; Wei Zhao; Xiaopeng Qi; Wanwei Sun; Chengjiang Gao
• Keywords: Antifungal Agents; QH301-705.5; Neutrophils; Ubiquitin-Protein Ligases; Candidiasis; RC581-607; Tripartite Motif Proteins; Mice; Neutrophil Infiltration; Candida albicans; Animals; Cytokines; Immunologic diseases. Allergy; Biology (General); Research Article

Fungal infections have emerged as a major concern among immunocompromised patients, causing approximately 2 million deaths each year worldwide. 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. Trim26-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 Candida 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 Trim26-deficient mice after Candida albicans 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.