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Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice
Published on: February 18, 2015
TRIM26 alleviates fatal immunopathology by regulating inflammatory neutrophil infiltration during Candida infection
Guimin Zhao1,2, Yanqi Li1,2, Tian Chen1,3
1Key Laboratory of Infection and Immunity of Shandong Province & Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong, P.R. China.
Abstract:
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.
Insights
The E3 ligase Trim26 plays a crucial role in antifungal immunity by limiting inflammatory responses. Trim26 deficiency increases susceptibility to fungal infections like candidiasis.
Area of Science:
- Immunology
- Molecular Biology
- Mycology
Background:
- Fungal infections pose a significant threat, especially to immunocompromised individuals, causing millions of deaths annually.
- Understanding the regulation of antifungal immunity is critical for developing effective treatments.
- The E3 ligase Trim26 (tripartite motif-containing protein 26) is implicated in various immune responses.
Purpose of the Study:
- To investigate the role of Trim26 in antifungal immunity.
- To elucidate the mechanisms by which Trim26 influences the host response to fungal infections.
Main Methods:
- Utilized Trim26-deficient mice and wild-type counterparts for comparative studies.
- Infected mice with Candida species to assess susceptibility and immune responses.
- Analyzed neutrophil infiltration, cytokine and chemokine production, and fungal load in kidneys.
- Assessed neutrophil fungicidal activity and cytokine expression in vitro.
Main Results:
- Trim26-deficient mice exhibited increased susceptibility to fungemia and candidiasis.
- Trim26 restricted excessive inflammatory neutrophil infiltration and proinflammatory cytokine production in the kidneys.
- Trim26 deficiency led to elevated levels of chemokines CXCL1 and CXCL2, promoting neutrophil recruitment.
- Trim26-deficient neutrophils displayed impaired fungicidal activity and heightened proinflammatory cytokine expression.
Conclusions:
- Trim26 is essential for protective antifungal immunity against Candida infection.
- Trim26 regulates antifungal responses by controlling inflammatory neutrophil infiltration and cytokine/chemokine expression.
- Targeting Trim26 could offer a novel therapeutic strategy for managing fungal infections.
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