ArticleCellular and molecular life sciences : CMLS2026
TRIM26-mediated regulation of TRAF6 ubiquitination enhances host immune response during Toxoplasma gondii infection.
Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Toxoplasma gondii is a parasitic protozoan that poses a significant threat to both human and livestock. Currently, effective control measures remain elusive, largely due to the unclear mechanisms underlying T. gondii infection and the host immune response. This study aims to elucidate the role of tripartite motif-containing 26 (TRIM26) in modulating the host immune response to T. gondii via regulating tumor necrosis factor receptor-associated factor 6 (TRAF6). Our findings revealed that T. gondii infection significantly upregulates TRIM26 expression in murine macrophages. Notably, TRIM26 acts as a novel regulator of TRAF6 by reducing K48-linked polyubiquitination of TRAF6, which in turn promotes the expression of downstream cytokines. This indicates that TRIM26 plays a critical role in the host immune response against T. gondii. Furthermore, in vivo investigations demonstrated that TRIM26 expression is upregulated during T. gondii infection. Additionally, Trim26−/− mice exhibited significantly reduced proportions of macrophages, inflammatory monocytes in ascites, and T cells in the spleen following infection. These knockout mice also exhibited reduced survival rates, decreased levels of IL-12, IFN-γ, and TNF-α, more severe organ pathological damage, and markedly higher parasite burdens compared to wild-type mice. Collectively, this study highlights the role of TRIM26 in regulating TRAF6 ubiquitination, enriches our understanding of the mechanism of TRAF6 modification. Additionally, it elucidates the significance of TRIM26 in the host immune response to T. gondii, and providing new insights and potential targets for the prevention and treatment of toxoplasmosis.
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