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

基本信息

批准号：
8464792
负责人：
Sarah E Hochman
金额：
$ 14.92万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-23 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8464792
关键词：
Address Adhesions Affect Africa South of the Sahara African Animal Model Antibodies Astrocytes Binding Blood - brain barrier anatomy Brain C57BL/6 Mouse CD4 Lymphocyte Count CD4 Positive T Lymphocytes Cause of Death Cell Communication Cells Cerebral Malaria Cessation of life Child Clinical Clinical Course of Disease Clinical Treatment Cognitive Coma Complex Data Dementia Development Disease Endothelial Cells Endothelium Erythrocytes Evaluation Experimental Models Goals HIV HIV Infections HIV Seropositivity HIV-1 Human Human immunodeficiency virus test Immune Immune Cell Activation Immune System Diseases Immune response Immune system Impairment In Vitro Individual Infection Inflammation Inflammation Mediators Inflammatory Response Intervention Lead Lymphocyte Malaria Mediating Minor Modeling Molecular Mononuclear Mus Myeloid Cells Neurocognitive Neurologic Organ Outcome Parasitemia Pathogenesis Pathology Peripheral Peripheral Blood Mononuclear Cell Permeability Plasmodium falciparum Production Proviruses Research Personnel Risk Rodent Model Severities Severity of illness Surface T-Lymphocyte Testing Time Transgenic Mice Vascular Endothelium Viral Load result Viremia Work brain cell cell motility cyclin T1 cytokine design effective therapy falls global health immune function improved in vitro Model in vivo inflammatory marker migration monocyte motor disorder mouse model novel patient population population based promoter public health relevance trafficking

项目摘要

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（调查员提供）：每年，由于疟疾而感染了5亿，死亡100万，大多数死亡是由于非洲儿童的脑疟疾而导致的。在撒哈拉以南非洲，大约有2440万人患有艾滋病毒，其中包括200万儿童。因此，数以百万计的人有与艾滋病毒和疟疾共同感染的风险，一种感染对另一种疾病病程的影响可能具有全球健康的影响。 HIV和疟疾各自与宿主的免疫系统相互作用，导致免疫细胞的复杂活化，随后严格调节细胞因子和抗体的产生。尽管早期基于人群的研究表明，HIV阳性和阴性疟疾的阴性个体之间的结局没有差异，但最近的工作表明，感染HIV的人在HIV患者中患有更频繁的症状性疟疾和疟疾发作会增加HIV病毒性血症并减少CD4+ T细胞。共同感染对CNS病理学的影响，包括脑疟疾和与HIV相关的神经认知障碍。我们假设HIV和疟疾共同感染加剧了宿主免疫反应，并且这种免疫失调解释了疾病临床范围的差异。在此提案中，我们将使用已建立的体外和体内实验模型来检查共同感染引起免疫失调的机制，以及这如何影响内皮激活和血脑屏障功能。