Autophagy induces apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV.

Autophagy induces apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV.
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自噬诱导猪瘟病毒感染猪脾脏中T淋巴细胞凋亡和死亡

DOI:
10.1038/s41598-017-14082-9
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发表时间:
2017-10-19
期刊:
影响因子:
4.6
通讯作者:
Chen J
Chen J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gou H;Zhao M;Fan S;Yuan J;Liao J;He W;Xu H;Chen J

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猪瘟病毒(CSFV)感染猪后,淋巴细胞减少和免疫功能低下是其典型的临床特征。猪瘟病毒感染细胞和旁观细胞的凋亡在猪瘟的免疫病理学中起重要作用。在这里,我们提供了第一个证据表明,自噬是参与细胞凋亡和死亡的T淋巴细胞在感染猪瘟病毒的猪脾脏。使用免疫组化检测,我们观察到更多的LC 3 II阳性细胞出现在脾脏的T细胞区。流式细胞术和TUNEL染色显示脾细胞凋亡。共聚焦免疫荧光显示,部分LC 3 II阳性细胞同时TUNEL阳性。通过体内脾细胞培养,我们证明了3-MA处理抑制自噬可抑制CSFV感染引起的T淋巴细胞凋亡和死亡,但对B淋巴细胞没有这种作用。进一步的观察表明,脾脏中未感染的细胞也在体内进行自噬。总之,这些结果将自噬与脾T细胞的凋亡和细胞死亡联系起来,为理解CSF中T淋巴细胞耗竭和免疫抑制的机制提供了新的前景。
Lymphocyte depletion and immunosuppression are typical clinical characteristics of pigs infected with classical swine fever virus (CSFV). The apoptosis of virus-infected and bystander cells plays a role in the immunopathology of classical swine fever (CSF). Here, we offer the first evidence that autophagy is involved in apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV. Using immunohistochemical assays, we observed that more LC3II-positive cells appear in the T-cell zone of spleens. Spleen cell apoptosis was demonstrated using flow cytometry and TUNEL staining. Confocal immunofluorescence revealed that partial LC3II-positive cells were simultaneously TUNEL-positive. By cultivating spleen cellsex vivo, we demonstrated that the inhibition of autophagy by 3-MA treatment inhibited apoptosis and death of T lymphocytes caused by CSFV infection but did not have this effect  on B lymphocytes. Further observations demonstrated that uninfected cells in the spleen were also undergoing autophagyin vivo. In summary, these results linked autophagy with the apoptosis and cell death of splenic T cells, providing a new outlook to understand the mechanism of T lymphocyte depletion and immunosuppression during CSF.
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