PRAK Promotes the Pathogen Clearance by Macrophage Through Regulating Autophagy and Inflammasome Activation.

PRAK Promotes the Pathogen Clearance by Macrophage Through Regulating Autophagy and Inflammasome Activation.
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DOI:
10.3389/fimmu.2021.618561
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发表时间:
2021
影响因子:
7.3
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学2区
文献类型:
--
作者:
Mi L;Wang Y;Xu H;Wang Y;Wu J;Dai H;Zhang Y

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p38调节/活化蛋白激酶(PRAK)是p38MAPK下游的一种蛋白激酶。本研究探讨了其在巨噬细胞中的作用。髓系特异性缺失Prak导致F4/80+CD11b+腹膜巨噬细胞显著减少,MHC-II和CD80的表达降低。在感染单核细胞增生李斯特菌后,prak缺陷小鼠的死亡率增加,这伴随着多个组织中较高的细菌负荷和血清中促炎细胞因子水平升高。虽然prak缺陷巨噬细胞在吞噬实验中表现出相似的效力,但其杀菌活性严重受损。此外,Prak缺乏与ROS生成、炎性体激活和自噬诱导缺陷有关。因此,PRAK通过影响巨噬细胞功能的多个方面对细胞内病原体的清除起着至关重要的作用。
The p38 regulated/activated protein kinase (PRAK) is a protein kinase downstream of p38MAPK. The present study investigated its function in the macrophage. Myeloid-specific deletion of Prak resulted in a significant reduction in F4/80+CD11b+ peritoneal macrophages with decreased expression of MHC-II and CD80. Upon infection with Listeria monocytogenes, Prak-deficient mice demonstrated an increased mortality, which was accompanied by a higher bacterial load in multiple tissues and elevated levels of proinflammatory cytokines in the serum. While the Prak-deficient macrophage showed similar potency in phagocytosis assays, its bactericidal activity was severely impaired. Moreover, Prak deficiency was associated with defects in ROS production, inflammasome activation as well as autophagy induction. Therefore, PRAK critically contributes to the clearance of intracellular pathogens by affecting multiple aspects of the macrophage function.
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