HIV/Malaria Coinfection Effects on Immune Dysfunction and the Blood-Brain Barrier

HIV/疟疾混合感染对免疫功能障碍和血脑屏障的影响

• 批准号: 9134372
• 负责人: Sarah E Hochman
• 金额: $ 5.42万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-23 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134372
• 关键词: HIV; Malaria; Coinfection; Effects; Immune

DESCRIPTION (provided by investigator): Each year, 500 million are infected and 1 million die because of malaria, with most deaths due to cerebral malaria in African children. In sub-Saharan Africa, roughly 24.4 million people have HIV, including 2 million children. Thus, millions are at risk for coinfection with both HIV and malaria, and effects of one infection on the disease course of the other may have global health implications. HIV and malaria each interact with the host's immune system uniquely, resulting in complex activations of immune cells, and subsequent tightly regulated production of cytokines and antibodies. While early population-based studies showed no difference in outcomes between HIV-positive and negative individuals with malaria, more recent work suggests HIV-infected people have more frequent episodes of symptomatic malaria and malaria in those with HIV increases HIV viremia and decreases CD4+ T cells. The effects of co-infection on CNS pathology, including cerebral malaria and HIV-associated neurocognitive disorders, are not known. We hypothesize that HIV and malaria co-infection exacerbates the host immune response, and that this immune dysregulation explains differences in the clinical spectrum of disease. In this proposal, we will use established in vitro and in vivo experimental models to examine the mechanisms by which co-infection causes immune dysregulation and how this impacts endothelial activation and blood-brain barrier function.

描述（由调查员提供）：每年有 5 亿人感染疟疾，100 万人死于疟疾，其中大多数死亡是非洲儿童死于脑疟疾。在撒哈拉以南非洲地区，大约有 2440 万人感染艾滋病毒，其中包括 200 万儿童。因此，数百万人面临同时感染艾滋病毒和疟疾的风险，并且一种感染对另一种感染病程的影响可能会对全球健康产生影响。 HIV和疟疾与宿主免疫系统的相互作用各不相同，导致免疫细胞的复杂激活，以及随后严格调节的细胞因子和抗体的产生。虽然早期基于人群的研究表明，HIV 阳性和阴性疟疾患者之间的结果没有差异，但最近的研究表明，HIV 感染者有症状的疟疾发作更频繁，而 HIV 感染者的疟疾会增加 HIV 病毒血症并减少 CD4+ T 细胞。合并感染对中枢神经系统病理学的影响，包括脑型疟疾和艾滋病毒相关的神经认知障碍，尚不清楚。 我们假设艾滋病毒和疟疾共同感染会加剧宿主的免疫反应，这种免疫失调解释了疾病临床谱的差异。在本提案中，我们将利用已建立的体外和体内实验模型来研究联合感染导致免疫失调的机制以及这如何影响内皮激活和血脑屏障功能。