國家衛生研究院 NHRI:Item 3990099045/14882
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/14882


    Title: CLEC5A mediates Zika virus-induced testicular damage
    Authors: Wang, HW;Li, HH;Wu, SC;Tang, CK;Yu, HY;Chang, YC;Sung, PS;Liu, WL;Su, MP;Yu, GY;Huang, LR;Chen, CH;Hsieh, SL
    Contributors: Immunology Research Center;Institute of Molecular and Genomic Medicine;National Institute of Infectious Diseases and Vaccinology;National Mosquito-Borne Diseases Control Research Center
    Abstract: Background: Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially 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 investigated 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 spermatozoon 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 pathogenesis 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 function, 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.
    Date: 2023-02-17
    Relation: Journal of Biomedical Science. 2023 Feb 17;30:Article number 12.
    Link to: http://dx.doi.org/10.1186/s12929-023-00906-6
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=10217-7770&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000935913800001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85148390083
    Appears in Collections:[Shie-Liang Hsieh] Periodical Articles
    [Li-Rung Huang] Periodical Articles
    [Chun-Hong Chen] Periodical Articles
    [Guann-Yi Yu] Periodical Articles
    [Others] Periodical Articles

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