{"title":"幽门螺杆菌延缓中性粒细胞凋亡,但也驱动具有渗漏质膜的细胞的形成:对炎症的影响","authors":"Tran Duong Thai , Chatcharin Kamsom , Wisitsak Phoksawat , Arnone Nithichanon , Kiatichai Faksri , Banchob Sripa , Steven W. Edwards , Kanin Salao","doi":"10.1016/j.molimm.2025.05.006","DOIUrl":null,"url":null,"abstract":"<div><div><em>Opisthorchis viverrini</em> (OV)-induced cholangiocarcinoma (CCA) is a significant public health concern in countries in the Lower Mekong Basin. OV is a reservoir for <em>Helicobacter pylori</em> (<em>H. pylori</em>), and so many individuals are co-infected with these two biological carcinogens. Our study aimed to investigate interactions between <em>H. pylori</em> isogenic strains possessing or lacking the pathogenicity factor CagA (<em>cag</em>A+ and <em>cag</em>A-) with neutrophils. Both <em>H. pylori</em> strains were co-cultured with neutrophils <em>in vitro</em>, and neutrophil activation, phagocytosis, reactive oxygen species (ROS) production, and cell survival/apoptosis were measured. Both isogenic strains of <em>H. pylori</em> stimulated phagocytosis and while the <em>cag</em>A- strain induced slightly higher ROS production, both strains served as potent activators of neutrophils. Notably, <em>H. pylori</em> induced rapid cell death in a sub-population of neutrophils after 30 min of co-incubation while extending the lifespan of the neutrophils that survived this initial cell death. This initial incubation resulted in the appearance of propidium iodide (PI)+ neutrophils, i.e. cells with a compromised plasma membrane that could result in the release of inflammation-promoting neutrophil contents. While significantly more viable neutrophils were detected after 24 h (and 48 h) incubation with <em>H. pylori</em>, those cells that did not survive also showed characteristics of a compromised plasma membrane (i.e. PI+). We propose that the combinations of PI+ neutrophils with leaky plasma membranes and non-apoptotic neutrophils with enhanced survival after incubation with <em>H. pylori</em> may drive persistent inflammation. These findings offer new insights into the immunopathogenesis of OV and <em>H. pylori</em> co-infections, which may help improve OV treatment strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"183 ","pages":"Pages 236-245"},"PeriodicalIF":3.0000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Helicobacter pylori delays neutrophil apoptosis but also drives the formation of cells with a leaky plasma membrane: Implications for inflammation\",\"authors\":\"Tran Duong Thai , Chatcharin Kamsom , Wisitsak Phoksawat , Arnone Nithichanon , Kiatichai Faksri , Banchob Sripa , Steven W. Edwards , Kanin Salao\",\"doi\":\"10.1016/j.molimm.2025.05.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div><em>Opisthorchis viverrini</em> (OV)-induced cholangiocarcinoma (CCA) is a significant public health concern in countries in the Lower Mekong Basin. OV is a reservoir for <em>Helicobacter pylori</em> (<em>H. pylori</em>), and so many individuals are co-infected with these two biological carcinogens. Our study aimed to investigate interactions between <em>H. pylori</em> isogenic strains possessing or lacking the pathogenicity factor CagA (<em>cag</em>A+ and <em>cag</em>A-) with neutrophils. Both <em>H. pylori</em> strains were co-cultured with neutrophils <em>in vitro</em>, and neutrophil activation, phagocytosis, reactive oxygen species (ROS) production, and cell survival/apoptosis were measured. Both isogenic strains of <em>H. pylori</em> stimulated phagocytosis and while the <em>cag</em>A- strain induced slightly higher ROS production, both strains served as potent activators of neutrophils. Notably, <em>H. pylori</em> induced rapid cell death in a sub-population of neutrophils after 30 min of co-incubation while extending the lifespan of the neutrophils that survived this initial cell death. This initial incubation resulted in the appearance of propidium iodide (PI)+ neutrophils, i.e. cells with a compromised plasma membrane that could result in the release of inflammation-promoting neutrophil contents. While significantly more viable neutrophils were detected after 24 h (and 48 h) incubation with <em>H. pylori</em>, those cells that did not survive also showed characteristics of a compromised plasma membrane (i.e. PI+). We propose that the combinations of PI+ neutrophils with leaky plasma membranes and non-apoptotic neutrophils with enhanced survival after incubation with <em>H. pylori</em> may drive persistent inflammation. These findings offer new insights into the immunopathogenesis of OV and <em>H. pylori</em> co-infections, which may help improve OV treatment strategies.</div></div>\",\"PeriodicalId\":18938,\"journal\":{\"name\":\"Molecular immunology\",\"volume\":\"183 \",\"pages\":\"Pages 236-245\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0161589025001269\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161589025001269","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Helicobacter pylori delays neutrophil apoptosis but also drives the formation of cells with a leaky plasma membrane: Implications for inflammation
Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is a significant public health concern in countries in the Lower Mekong Basin. OV is a reservoir for Helicobacter pylori (H. pylori), and so many individuals are co-infected with these two biological carcinogens. Our study aimed to investigate interactions between H. pylori isogenic strains possessing or lacking the pathogenicity factor CagA (cagA+ and cagA-) with neutrophils. Both H. pylori strains were co-cultured with neutrophils in vitro, and neutrophil activation, phagocytosis, reactive oxygen species (ROS) production, and cell survival/apoptosis were measured. Both isogenic strains of H. pylori stimulated phagocytosis and while the cagA- strain induced slightly higher ROS production, both strains served as potent activators of neutrophils. Notably, H. pylori induced rapid cell death in a sub-population of neutrophils after 30 min of co-incubation while extending the lifespan of the neutrophils that survived this initial cell death. This initial incubation resulted in the appearance of propidium iodide (PI)+ neutrophils, i.e. cells with a compromised plasma membrane that could result in the release of inflammation-promoting neutrophil contents. While significantly more viable neutrophils were detected after 24 h (and 48 h) incubation with H. pylori, those cells that did not survive also showed characteristics of a compromised plasma membrane (i.e. PI+). We propose that the combinations of PI+ neutrophils with leaky plasma membranes and non-apoptotic neutrophils with enhanced survival after incubation with H. pylori may drive persistent inflammation. These findings offer new insights into the immunopathogenesis of OV and H. pylori co-infections, which may help improve OV treatment strategies.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.