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感染通过调节宿主细胞线粒体功能和自噬,特异性抑制宿主长链非编码RNA的表达,以促进寄生虫繁殖。

infection specifically suppresses the expression of a host lncRNA to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy.

作者信息

Zhao Shan-Shan, Tao De-Liang, Chen Jin-Ming, Zhang Ming-Yi, Yang Xin, Song Jun-Ke, Liu Qun, Zhao Guang-Hui

机构信息

Department of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.

出版信息

Microbiol Spectr. 2025 Feb 4;13(2):e0158024. doi: 10.1128/spectrum.01580-24. Epub 2024 Dec 23.

DOI:10.1128/spectrum.01580-24
PMID:39714178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11792476/
Abstract

is one of the most common pathogens causing reproductive failure in ruminants (e.g., cattle and goats) worldwide. However, due to a poor understanding of the pathogenic mechanisms of infection, no effective drugs and vaccines are currently available. Long non-coding RNAs (lncRNAs) have been reported to be important regulators involved in a great number of physiological and pathological processes. Our previous study found that infection induced significantly aberrant expression of lncRNA profiles in caprine endometrial epithelial cells (EECs). In the present study, we found that infection specifically suppressed the expression of a novel lncRNA, , and knockdown of with small interfering RNA significantly promoted the propagation of in caprine EECs. Rapid amplification of cDNA ends analysis generated six splice variants of , with lengths ranging from 592 to 694 nt. Transfection of the full length of each variant markedly inhibited the propagation of in caprine EECs. Further study suggested that acted as a sponge of Chi-miR-93-5p to promote the expression of , and the /Chi-miR-93-5p/ axis significantly delayed the growth of in caprine EECs by regulating host cell mitochondrial function and autophagy. Our findings provide a novel insight to understand the interactions between and host cells.IMPORTANCEThe uterus is an indispensable reproductive organ for embryo implantation and fetal growth. The endometrium is more vulnerable to infection by pathogenic microorganisms resulting in an increased risk of miscarriage. is one of the most common pathogens causing miscarriage in ruminants and is able to naturally inhabit the uterus, with tissue cysts found in the endometrium. Recent advances in research have revealed aberrant expression of long non-coding RNA (lncRNA) profiles in infected caprine endometrial epithelial cells. In the present study, , but not which has similar morphological and biological features to , specifically suppresses the expression of a host lncRNA, , to impair host's defense through the competitive endogenous RNA mechanism to modulate the host cell mitochondrial function and autophagy to facilitate parasite propagation. The findings suggest a novel immune evasion strategy of to facilitate intracellular propagation and provide an alternative path to develop control strategies against neosporosis.

摘要

是全球反刍动物(如牛和山羊)繁殖失败的最常见病原体之一。然而,由于对感染的致病机制了解不足,目前尚无有效的药物和疫苗。据报道,长链非编码RNA(lncRNA)是参与大量生理和病理过程的重要调节因子。我们之前的研究发现,感染可诱导山羊子宫内膜上皮细胞(EECs)中lncRNA谱的显著异常表达。在本研究中,我们发现感染特异性抑制了一种新型lncRNA即 的表达,用小干扰RNA敲低 可显著促进 在山羊EECs中的增殖。cDNA末端快速扩增分析产生了 的六个剪接变体,长度范围为592至694 nt。转染每个变体的全长可显著抑制 在山羊EECs中的增殖。进一步研究表明, 作为Chi-miR-93-5p的海绵来促进 的表达,并且 /Chi-miR-93-5p/ 轴通过调节宿主细胞线粒体功能和自噬显著延迟了 在山羊EECs中的生长。我们的研究结果为理解 与宿主细胞之间的相互作用提供了新的见解。

重要性

子宫是胚胎着床和胎儿生长不可或缺的生殖器官。子宫内膜更容易受到病原微生物的感染,导致流产风险增加。 是反刍动物流产的最常见病原体之一,能够自然栖息在子宫内,在子宫内膜中发现有 组织囊肿。 研究的最新进展揭示了感染山羊子宫内膜上皮细胞中长链非编码RNA(lncRNA)谱的异常表达。在本研究中, 而非与 具有相似形态和生物学特征的 ,特异性抑制宿主lncRNA即 的表达,通过竞争性内源RNA机制损害宿主防御,调节宿主细胞线粒体功能和自噬以促进寄生虫繁殖。这些发现提示了 促进细胞内繁殖的一种新的免疫逃避策略,并为开发针对新孢子虫病的控制策略提供了一条替代途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061f/11792476/b1916a554931/spectrum.01580-24.f010.jpg
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