Novel vacuole biology in chronic Toxoplasma infection

慢性弓形虫感染中的新型液泡生物学

• 批准号: 10092083
• 负责人: DAVID J BZIK
• 金额: $ 24.6万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-04 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092083
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Antigen Presentation; Antigens; Appearance; Biological Assay; Biology; CD8-Positive T-Lymphocytes; Cells; Cessation of life; Chronic; Clinical; Clinical Management; Complex; Cyst; Data; Development; Encephalitis; Family; Gene Deletion; Genetic; Granzyme; Growth; Histocompatibility; Hospitalization; Immune; In Vitro; Infection; Interferons; Maintenance; Measures; Mediating; Medical; Membrane; Microglia; Morphology; Mutation; Natural Immunity; Neuraxis; Oocysts; Oral; Oral Ingestion; Parasites; Patients; Penetration; Phase; Phenotype; Phosphotransferases; Play; Population; Proteins; Reporting; Resistance; Role; Structure; T cell response; T-Lymphocyte; Testing; Toxoplasma; Toxoplasma gondii; United States; Vacuole; Virulence; base; chronic infection; foodborne pathogen; in vivo; insight; macrophage; member; mutant; novel; oral infection; perforin; pressure; prevent; protein complex; rhoptry; toxoplasmic encephalitis

Abstract Oral ingestion of Toxoplasma gondii cysts establishes a chronic infection marked by the development of cysts in the central nervous system. Reactivation of dormant Toxoplasma gondii cysts in the central nervous system in AIDS patients causes Toxoplasmic encephalitis, a clinically difficult to treat and frequently lethal encephalitis. The parasite factors that enable the chronic persistence and oral infectivity of cysts are still poorly understood. We hypothesize that the ROP35 kinase and other members of the Toxoplasma gondii WNG kinase family play important roles in maintaining persisting cysts and their oral infectivity. This study will characterize the role of ROP35 in mediating successful chronic infection, and the role of WNG kinases, and their protein complexes, that enable the persistence of viable and orally infectious Toxoplasma gondii cysts.

抽象的 口服摄入弓形虫包囊会形成慢性感染，其特征是出现 中枢神经系统的囊肿。中枢神经中休眠的弓形虫包囊的重新激活 艾滋病患者的系统会导致弓形虫脑炎，这是一种临床上难以治疗且常常致命的疾病 脑炎。导致囊肿长期持续存在并具有口腔感染性的寄生虫因素仍然存在 不太了解。我们假设 ROP35 激酶和弓形虫的其他成员 WNG 激酶家族在维持包囊持续存在及其口腔感染性方面发挥着重要作用。这项研究 将描述 ROP35 在成功介导慢性感染中的作用以及 WNG 激酶的作用， 及其蛋白质复合物，使活的和口腔感染性弓形虫能够持久存在 囊肿。