Platelet Mediated Immune Responses in Experimental Cerebral Malaria

实验性脑型疟疾中血小板介导的免疫反应

基本信息

批准号：
8257469
负责人：
Angela A Aggrey
金额：
$ 4.22万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8257469
关键词：
Acute-Phase Proteins Acute-Phase Reaction Adult Alternative Therapies Anemia Area Binding Blood Platelets Blood Vessels C-reactive protein CD36 gene Cell Therapy Cells Cerebral Malaria Cerebrum Characteristics Child Clinical Research Coagulation Process Complement Complication Conflict (Psychology)Country Deposition Disease Progression Environment Enzyme-Linked Immunosorbent Assay Erythrocytes Fibrinolysis Flow Cytometry Funding Future Generations Human Immune Immune response In Vitro Infection Inflammation Inflammatory Interleukin-1 Knockout Mice Lead Leukocytes Malaria Mediating Modeling Mus Outcome Parasites Pathogenesis Pathology Patients Pharmacologic Substance Plasma Plasmodium Plasmodium falciparum Platelet Activation Platelet Inhibitors Production Protein Binding Proteins Reaction Reporting Role Serum amyloid A protein Staging Time Travel Vaccines Work cytokine in vivo interest killings novel protective effect receptor research study response vaccine development

项目摘要

DESCRIPTION (provided by applicant): Cerebral Malaria (CM) is an often fatal complication of Plasmodium falciparum infection. CM has a characteristic cerebral vascular pathology. Post-mortem analysis of CM patients show microvascular sequestration of platelets, infected red blood cells (iRBCs) as well as leukocytes. CM has thus been viewed by some as a mechano-obstructive pathology and by others, the result of prolonged immune stimulation leading to a pro-inflammatory state. Platelets have both vascular obstructive and pro-inflammatory effects and can thus bridge these seemingly opposing views of CM pathology. Previous studies have shown that platelets are directly activated by iRBCs and may contribute adversely to CM pathogenesis by promoting a pro-inflammatory environment within the cerebral microvasculature. Recently, platelets have been described as having the capacity in uncomplicated malaria to kill intraerythrocytic Plasmodium parasites. These somewhat conflicting roles for platelets in malaria infections provide further impetus to study the contributions of platelets to CM pathogenesis. In particular it is of great interest to study the potentially diametric functions of platelets during the course of disease progression and to demonstrate the capacity of platelets to act as innate immune cells. This application thus has two aims: 1) To demonstrate that iRBCs activate platelets and these activated platelets subsequently induce an early innate immune response and 2) to determine the specific mechanisms through which this occurs.

描述（由申请人提供）：脑型疟疾（CM）是恶性疟原虫感染的一种常见致命并发症。 CM 具有特征性的脑血管病理学。 CM 患者的尸检分析显示血小板、受感染的红细胞 (iRBC) 以及白细胞的微血管隔离。因此，一些人将 CM 视为一种机械阻塞性病理学，而另一些人则将其视为长期免疫刺激导致促炎状态的结果。血小板具有血管阻塞和促炎作用，因此可以弥合这些看似相反的 CM 病理学观点。先前的研究表明，血小板直接被 iRBC 激活，并可能通过促进脑微血管内的促炎环境而对 CM 发病机制产生不利影响。最近，血小板被描述为在无并发症的疟疾中具有杀死红细胞内疟原虫寄生虫的能力。血小板在疟疾感染中的这些有些矛盾的作用进一步推动了研究血小板对 CM 发病机制的贡献。特别是研究血小板在疾病进展过程中的潜在直接功能并证明血小板作为先天免疫细胞的能力非常令人感兴趣。因此，该应用有两个目的：1) 证明 iRBC 激活血小板，并且这些激活的血小板随后诱导早期先天免疫反应；2) 确定发生这种情况的具体机制。