頁籤選單縮合
題名 | CLEC5A Mediates Zika Virus-induced Testicular Damage |
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作者姓名(外文) | Wang, Hsin-wei; Li, Hsing-han; Wu, Shih-cheng; Tang, Cheng-kang; Yu, Hui-ying; Chang, Ya-chen; Sung, Pei-shan; Liu, Wei-liang; Su, Matthew P.; Yu, Guann-yi; Huang, Li-rung; Chen, Chun-hong; Hsieh, Shie-liang; | 書刊名 | Journal of Biomedical Science |
卷期 | 30 2023[民112] |
頁次 | 頁(12)1-(12)16 |
分類號 | 415.239 |
關鍵詞 | CLEC5A; Zika virus; Inflammation; Testicular damage; Mouse; Mosquito; |
語文 | 英文(English) |
DOI引用網址 | 10.1186/s12929-023-00906-6 |
英文摘要 | Background Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and poten‑ tially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C‑type lectins play important roles in mediating virus‑induced inflammatory reactions and pathogenesis. We thus investi‑ gated whether C‑type lectins modulate ZIKV‑induced testicular damage. Methods C‑type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1‑deficient immunocompromised background (denoted clec5a−/− stat1−/−) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito‑to‑mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT‑PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermato‑ zoon counting. Furthermore, DNAX‑activating proteins for 12 kDa (DAP12) knockout mice (dap12−/− stat1−/−) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A. Results Compared to experiments conducted in ZIKV‑infected stat1−/− mice, infected clec5a−/− stat1−/− mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the patho‑ genesis of ZIKV‑induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5a−/− stat1−/− mice. As for CLEC5A deficient mice, ZIKV‑infected DAP12‑deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa func‑ tion, as compared to controls. CLEC5A‑associated DAP12 signaling appears to in part regulate ZIKV‑induced testicular damage. Conclusions Our analyses reveal a critical role for CLEC5A in ZIKV‑induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood‑testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients. |
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