MECHANISMS OF ERYTHROCYTIC INFECTIONS AND ANEMIA: NHP MODEL MALARIAL ANEMIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该计划项目的总体目标是了解疟疾寄生虫感染红细胞并在哺乳动物宿主中引起贫血的分子和细胞机制。该项目的主要目标是建立非人类灵长类贫血模型。为了实现这些目标，一群在血液学、寄生虫学、细胞生物学、生物化学、分子生物学、免疫学、寄生虫遗传学、功能基因组学、啮齿动物和非人类灵长类动物模型方面具有专业知识的研究人员聚集在一起，共同努力。 预计这一方案将导致制定防治疟疾感染和贫血的治疗策略。到目前为止，我们已经建立和完善了一种动物模型，用于研究恶性疟原虫贫血的生理学，使用恒河猴/Coatneyi模型系统，是检测感染的血液和骨髓样本的理想模型。在过去的一年里，通过改进方案，在一组恒河猴中完成了连续的Coatneyi感染，以建立初生猴和随后的半免疫动物的贫血过程以及疾病和恢复的机制。将需要进行后续的免疫学和组织病理学分析。 与这些感染有关的手稿正在准备中，并正在计划以类似的方式建立食蟹猴-恒河猴模型来研究间日疟原虫贫血。这种活体模型远比小鼠模型更可取，它一直在提供与理解人类严重疟疾的多因素原因相关的关键和独特的见解。该项目的资金支持也促进了其他几项基本的血液阶段研究，一系列手稿正在准备中。 还发表了一篇综述，突出了间日疟原虫和食蟹猴疟疾模型对研究这种广泛存在的人类疟疾寄生虫的生物学和发病机制的重要性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective of this program project has been to develop an understanding of the molecular and cellular mechanisms by which malaria parasites infect erythrocytes and induce anemia in their mammalian hosts. The main objective of this project is to establish non-human primate models of anemia. To achieve these objectives a group of investigators with expertise in hematology, parasitology, cell biology, biochemistry, molecular biology, immunology, parasite genetics, functional genomics, rodent and non-human primate models came together to mount a concerted effort. This program has been expected to lead to the development of therapeutic strategies against malarial infection and anemia. To date, we have established and refined an animal model to study the physiology of P. falciparum malarial anemia using the rhesus monkey / P. coatneyi model system; an ideal model to examine infected blood and bone marrow samples. This past year, consecutive P. coatneyi infections were completed in a group of rhesus monkeys with refined protocols, to establish the course of anemia and mechanisms of disease and recovery in both na¿ve and subsequently semi-immune animals. Follow-up immunological and histopathological analyses will be required. A manuscript relating to these infections has been in preparation and planning has been underway to similarly establish the P. cynomolgi - rhesus model to study P. vivax malaria anemia. This in vivo model, which is far preferable to a mouse model, has been providing critical and unique insights relevant to understanding the multi-factorial causes of severe malaria disease in humans. Several other basic blood-stage studies have also been facilitated by the funding support of this project, and a series of manuscripts are in preparation. A review has also been published which highlights P. vivax and the importance of the P. cynomolgi simian malaria model for studying the biology and pathogenesis of this widespread human malaria parasite.