Helicobacter pylori CagA mediated mitophagy to attenuate the NLRP3 inflammasome activation and enhance the survival of infected cells.

Autor: Chen D; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China.; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Wu L; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China., Liu X; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China., Wang Q; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China., Gui S; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China., Bao L; Hepatitis Laboratory, Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China., Wang Z; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China., He X; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China., Zhao Y; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China. 501155185@qq.com., Zhou J; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China. jianjiangzhou@sina.cn., Xie Y; Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China. 37408126@qq.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Sep 17; Vol. 14 (1), pp. 21648. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1038/s41598-024-72534-5
Abstrakt: Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.
(© 2024. The Author(s).)
Databáze: MEDLINE
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