Assessing the impact of ABCA1 and ABCG1 expression on T. brucei infection

评估 ABCA1 和 ABCG1 表达对布氏锥虫感染的影响

• 批准号: 10886844
• 负责人: Alexis Stamatikos
• 金额: $ 22.85万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10886844
• 关键词: ATP binding cassette transporter 1; Adverse effects; African Trypanosomiasis; Anti-Inflammatory Agents; Centers of Research Excellence; Cessation of life; Cholesterol; Disease; Human; Immune response; Infection; Inflammatory; Left; Mediating; Membrane Microdomains; Parasites; Patients; Process; Toll-like receptors; Trypanosoma brucei brucei; Virulence; innovation; neglected tropical diseases; pathogen; side effect

Trypanosoma brucei is a kinetoplastid parasite that causes African trypanosomiasis disease in humans. African trypanosomiasis, also known as African sleeping sickness, is considered a neglected tropical disease. If left untreated, African sleeping sickness is 100% fatal. Treatments for African sleeping sickness are notorious for causing adverse effects in patients and some of the side effects can result in patient death. The transporters ABCA1 and ABCG1 function to remove intracellular cholesterol via participating in cholesterol efflux, resulting in the disruption of lipid-rafts. This process is anti-inflammatory, since activated toll-like receptors need to first translocate into lipid-rafts to trigger a pro-inflammatory immune response. Therefore, manipulating expression of ABCA1 and/or ABCG1 may influence parasite pathologenicity and virulence through modulating toll-like receptor-mediated activation upon T. brucei infection.

布氏锥虫是一种能引起人类非洲锥虫病的动质体寄生虫。非洲锥虫病，也被称为非洲昏睡病，被认为是一种被忽视的热带疾病。如果不及时治疗，非洲昏睡病是100%致命的。非洲昏睡病的治疗因对患者造成不良影响而臭名昭着，一些副作用可能导致患者死亡。转运蛋白ABCA 1和ABCG 1通过参与胆固醇流出而清除细胞内胆固醇，导致脂筏的破坏。这个过程是抗炎的，因为激活的toll样受体需要首先转移到脂筏中以触发促炎免疫应答。因此，操纵ABCA 1和/或ABCG 1的表达可能通过调节Toll样受体介导的T.布氏杆菌感染