Microsporidian obligate intracellular parasites subvert autophagy of infected mammalian host cells to promote their own growth
Microsporidian obligate intracellular parasites subvert autophagy of infected mammalian host cells to promote their own growth
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小孢子虫专性细胞内寄生虫破坏受感染哺乳动物宿主细胞的自噬以促进其自身生长
DOI：
10.1101/2022.08.15.503970
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Panek J
中科院分区：
文献类型：
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作者：
Panek J
细胞内的病原体，如微孢子虫，可以与宿主的蛋白平衡途径，如自噬相互作用。先前在秀丽隐杆线虫上所做的工作表明，自噬通过对寄生虫的泛素标记和随后的自溶体降解来参与控制微孢子虫的增殖。然而，目前尚不清楚这种机制是否也在哺乳动物模型中发挥作用。在这里，我们使用免疫化学分析，超分辨荧光显微镜，以及通过siRNA沉默和化学试剂调节宿主的自噬通量来阐明微孢子虫是如何与宿主哺乳动物细胞自噬通量相互作用的。我们发现，尽管以早期的自噬标志物(泛素和p62)为靶标，宿主细胞仍不能完成自噬介导的楔形脑孢子虫的清除。此外，自噬的诱导非但没有帮助控制微孢子虫的增殖，反而在两种不同的哺乳动物细胞模型中显著增加了两种微孢子虫的增殖。最后，我们表明，使用siRNA处理或肠道微生物区系衍生的代谢物减少自噬通量能够减少寄生虫的增殖，这些代谢物对肠上皮的动态平衡很重要。综上所述，我们的结果表明，感染哺乳动物细胞的微孢子虫不仅发展了逃避宿主自噬的策略，而且进化出了转移自噬通量以促进自身生长的方法。
Intracellular pathogens such as Microsporidia can interact with host proteostasis pathways such as autophagy. Previous work done inCaenorhabditis elegansdemonstrated involvement of autophagy in controlling Microsporidian proliferation through ubiquitin labelling of the parasite and subsequent degradation by autolysomes. However, it remains unknown if such mechanisms also play the role in mammalian models. Here we used immunochemistry assays, super-resolution fluorescence microscopy, and modulation of the host’s autophagy flux through siRNA silencing and chemical agents to elucidate how Microsporidia interact with host mammalian cell autophagy flux. We show that despite targeting by early autophagy markers (ubiquitin and p62); the host cell was not able to complete autophagy-mediated removal ofEncephalitozoon cuniculi. Furthermore, instead of helping to control Microsporidia proliferation, the induction of autophagy dramatically increased proliferation of two Microsporidian species in two different mammalian cell models. Finally, we showed that the reduction of the autophagy flux using siRNA treatment or gut microbiota-derived metabolites known to be important for the intestinal epithelium homeostasis was able to reduce the parasite proliferation. Taken together, our results indicate that Microsporidia infecting mammalian cells not only developed strategies to evade the host autophagy but also evolved way to divert the autophagy flux to promote their own growth.
DOI：
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发表时间：
2022
期刊：
CABI Compendium
影响因子：
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作者：
I. C. Barić;Z. Šatalić
通讯作者：
Z. Šatalić
1-( 4-( 4-丙酰哌嗪-1-基 )-3-( 三氟甲基 ) 苯基 )-9-( 喹啉-3-基 ) 苯并 [ h ] [ 1 , 6 ] naphthyridin-2 ( 1 H ) 的发现
DOI：
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发表时间：
2014
期刊：
影响因子：
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作者：
Qingsong Liu;J. Chang;Jun Wang;S. A. Kang;Catie Carson;Thoreen;Andrew L. Markhard;W. Hur;Jianming Zhang;Taebo Sim;David A. Mortensen;M. H. Sabatini;N. Gray
通讯作者：
N. Gray
影响因子：
6.7
作者：
Wadi, Lina;Reinke, Aaron W.
通讯作者：
Reinke, Aaron W.