https://ror.org/01kj4z117 The State Key Laboratory of Resource Insects, Southwest University, Chongqing, China
https://ror.org/01kj4z117 Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, China.
Life Sci Alliance. 2024 Jan 10;7(4). doi: 10.26508/lsa.202302375. Print 2024 Apr.
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. , one of the most commonly diagnosed zoonotic microsporidia species, was applied. In vivo models demonstrated that -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 infection impaired DCs' immune functions, reflected by down-regulated cytokine expressions, lower extent of maturation, phagocytosis ability, and antigen presentations. infection also detained DCs' potencies to prime and stimulate T cells; therefore, host immunities were disrupted. We found that 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.
微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 的损伤作用和后果。选择了一种最常见的诊断性动物源性微孢子虫种——来进行研究。体内模型表明，感染的小鼠更容易受到进一步的致病挑战，而 DC 被确定为受影响最严重的细胞群。体外实验表明，感染会损害 DC 的免疫功能，表现为细胞因子表达下调、成熟程度降低、吞噬能力和抗原呈递能力下降。感染还会抑制 DC 激活和刺激 T 细胞的能力，从而破坏宿主的免疫。我们发现，微孢子虫 Ser/Thr 蛋白磷酸酶 PP1 可直接与宿主 p38α（MAPK14）相互作用，从而操纵 MAPK 通路中的 p38α（MAPK14）/NFAT5 轴。本研究首次阐明了微孢子虫对宿主 DC 免疫功能的损伤作用的分子机制。微孢子虫病的出现可能对公众健康构成巨大威胁。
