p38 MAPK/MK2信号刺激宿主细胞的自途径,以限制沙门氏菌感染
Abdulhadi Suwandi1, Manoj B Menon2, Alexey Kotlyarov1
1Institute of Cell Biochemistry, Hannover Medical School, Hannover, Germany.
Frontiers in immunology
|September 29, 2023
概括
激活蛋白激酶 (MAPK) /激活蛋白激酶2 (MK2) 途径对宿主防御沙门氏菌至关重要. 它的抑制会损害自,增加细菌感染的易感性.
科学领域:
- 细胞微生物学 细胞微生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 自是一种关键的细胞防御机制,可以对抗像沙门氏菌这样的细胞内病原体.
- p38基因激活蛋白激酶 (MAPK) 途径与细胞应激反应和免疫有关.
研究的目的:
- 研究p38 MAPK/MK2通路对宿主细胞对沙门氏菌感染敏感性的作用.
- 阐明p38 MAPK/MK2通过自影响沙门氏菌清除的机制.
主要方法:
- 使用了沙门氏菌感染的小鼠胚胎纤维细胞 (MEF) 和MK2缺乏细胞.
- 采用西部斑分析来评估自标记物 (LC3脂化) 和关键酸化事件 (TANK结合激酶-1,p62/SQTM1).
- 进行了免疫光显微镜,以检查沙门氏菌与自蛋白的同位化 (LC3,p62).
- 在使用巴菲洛米辛A1.1.抑制自后评估的细菌负载.
主要成果:
- 抑制p38 MAPK或MK2显著增加了MEF中的沙门氏菌细菌数量.
- 缺乏MK2的细胞表现出LC3脂化减少,表明自功能受损.
- 在MK2缺乏细胞中观察到TANK结合激酶-1和p62/SQTM1的较低酸化,阻碍了p62转位和细菌自.
- 在缺乏MK2的MEF中显而易见的是,沙门氏菌与LC3和p62的局部化减少.
- 自抑制导致细菌负载增加,证实其在控制沙门氏菌中的作用.
结论:
- p38 MAPK/MK2通路在调节宿主细胞防御沙门氏菌感染方面发挥着至关重要的作用.
- p38 MAPK/MK2介导的酸化对于细胞内沙门氏菌的有效自是必不可少的,因为它促进了自途径中的关键步骤.
- 准p38 MAPK/MK2通路可能是一个新的治疗策略,以增强宿主对沙门氏菌的抵抗力.
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