C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis.

C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis.
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小鼠支持细胞响应腮腺炎病毒感染而产生的 C-X-C 基序趋化因子配体 10 诱导雄性生殖细胞凋亡。

DOI:
10.1038/cddis.2017.560
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发表时间:
2017-10-26
影响因子:
9
通讯作者:
Han D
Han D
中科院分区:
生物学1区
文献类型:
--
作者:
Jiang Q;Wang F;Shi L;Zhao X;Gong M;Liu W;Song C;Li Q;Chen Y;Wu H;Han D

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腮腺炎病毒(MuV)感染通常导致睾丸生殖细胞变性,这是男性不育的病因之一。然而,MuV感染损害男性生殖细胞的机制尚不清楚。本研究表明,小鼠Sertoli细胞对MuV感染产生C-X-C基序趋化因子配体10 (CXCL10),通过激活caspase-3诱导生殖细胞凋亡。CXC趋化因子受体3 (CXCR3)是CXCL10的一个功能性受体,在男性生殖细胞中组成性表达。中和CXCR3抗体和caspase-3激活抑制剂显著抑制cxcl10诱导的男性生殖细胞凋亡。此外,MuV感染后,肿瘤坏死因子-α (TNF-α)上调了支持细胞中CXCL10的产生。在MuV感染下,敲除CXCL10或TNF-α均可减少生殖细胞和支持细胞共培养中生殖细胞的凋亡。在小鼠睾丸局部注射MuV证实了CXCL10参与体内生殖细胞凋亡。这些结果为muv诱导的睾丸生殖细胞凋亡提供了新的见解。
Mumps virus (MuV) infection usually results in germ cell degeneration in the testis, which is an etiological factor for male infertility. However, the mechanisms by which MuV infection damages male germ cells remain unclear. The present study showed that C-X-C motif chemokine ligand 10 (CXCL10) is produced by mouse Sertoli cells in response to MuV infection, which induces germ cell apoptosis through the activation of caspase-3. CXC chemokine receptor 3 (CXCR3), a functional receptor of CXCL10, is constitutively expressed in male germ cells. Neutralizing antibodies against CXCR3 and an inhibitor of caspase-3 activation significantly inhibited CXCL10-induced male germ cell apoptosis. Furthermore, the tumor necrosis factor-α (TNF-α) upregulated CXCL10 production in Sertoli cells after MuV infection. The knockout of either CXCL10 or TNF-α reduced germ cell apoptosis in the co-cultures of germ cells and Sertoli cells in response to MuV infection. Local injection of MuV into the testes of mice confirmed the involvement of CXCL10 in germ cell apoptosis in vivo. These results provide novel insights into MuV-induced germ cell apoptosis in the testis.
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