E. hellem Ser/Thr 蛋白磷酸酶 PP1 靶向直流 MAPK 通路并损害免疫功能。

IF 3.3 2区 生物学 Q1 BIOLOGY
Life Science Alliance Pub Date : 2024-01-10 Print Date: 2024-04-01 DOI:10.26508/lsa.202302375
Jialing Bao, Yunlin Tang, Yebo Chen, Jiangyan Jin, Xue Wang, Guozhen An, Lu Cao, Huarui Zhang, Gong Cheng, Guoqing Pan, Zeyang Zhou
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引用次数: 0

摘要

小孢子虫一旦感染就很难被完全清除,其持续存在会破坏宿主细胞的功能。在本研究中,我们旨在阐明微孢子虫对宿主DC的损害作用和后果。研究应用了最常见的人畜共患微孢子虫之一螺旋体肠虫。体内模型显示,感染 hellem 肠孢子虫的小鼠更容易受到进一步的致病挑战,而 DC 被确定为受影响最大的细胞群。体外实验表明,鳗鲡感染会损害直流细胞的免疫功能,表现为细胞因子表达下调、成熟度降低、吞噬能力下降以及抗原呈递能力下降。E.hellem感染还抑制了DCs刺激T细胞的能力,从而破坏了宿主的免疫功能。我们发现, hellem E. Ser/Thr蛋白磷酸酶PP1直接与宿主p38α(MAPK14)相互作用,操纵MAPK通路的p38α(MAPK14)/NFAT5轴。我们的研究首次阐明了微孢子虫损害宿主DC免疫功能的分子机制。微孢子虫病的出现可能会对公共卫生造成巨大威胁。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
E. hellem Ser/Thr protein phosphatase PP1 targets the DC MAPK pathway and impairs immune functions.

Microsporidia are difficult to be completely eliminated once infected, and the persistence disrupts host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia on host DCs. Enterocytozoon hellem, one of the most commonly diagnosed zoonotic microsporidia species, was applied. In vivo models demonstrated that E. hellem-infected mice were more susceptible to further pathogenic challenges, and DCs were identified as the most affected groups of cells. In vitro assays revealed that E. hellem infection impaired DCs' immune functions, reflected by down-regulated cytokine expressions, lower extent of maturation, phagocytosis ability, and antigen presentations. E. hellem infection also detained DCs' potencies to prime and stimulate T cells; therefore, host immunities were disrupted. We found that E. hellem Ser/Thr protein phosphatase PP1 directly interacts with host p38α (MAPK14) to manipulate the p38α(MAPK14)/NFAT5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs' immune functions. The emergence of microsporidiosis may be of great threat to public health.

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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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