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用非人类灵长类动物探索疟疾的系统生物学。

Systems biology of malaria explored with nonhuman primates.

机构信息

Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Emory Vaccine Center, Emory University, Atlanta, GA, USA.

出版信息

Malar J. 2022 Jun 7;21(1):177. doi: 10.1186/s12936-022-04199-2.


DOI:10.1186/s12936-022-04199-2
PMID:35672852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9172618/
Abstract

"The Primate Malarias" book has been a uniquely important resource for multiple generations of scientists, since its debut in 1971, and remains pertinent to the present day. Indeed, nonhuman primates (NHPs) have been instrumental for major breakthroughs in basic and pre-clinical research on malaria for over 50 years. Research involving NHPs have provided critical insights and data that have been essential for malaria research on many parasite species, drugs, vaccines, pathogenesis, and transmission, leading to improved clinical care and advancing research goals for malaria control, elimination, and eradication. Whilst most malaria scientists over the decades have been studying Plasmodium falciparum, with NHP infections, in clinical studies with humans, or using in vitro culture or rodent model systems, others have been dedicated to advancing research on Plasmodium vivax, as well as on phylogenetically related simian species, including Plasmodium cynomolgi, Plasmodium coatneyi, and Plasmodium knowlesi. In-depth study of these four phylogenetically related species over the years has spawned the design of NHP longitudinal infection strategies for gathering information about ongoing infections, which can be related to human infections. These Plasmodium-NHP infection model systems are reviewed here, with emphasis on modern systems biological approaches to studying longitudinal infections, pathogenesis, immunity, and vaccines. Recent discoveries capitalizing on NHP longitudinal infections include an advanced understanding of chronic infections, relapses, anaemia, and immune memory. With quickly emerging new technological advances, more in-depth research and mechanistic discoveries can be anticipated on these and additional critical topics, including hypnozoite biology, antigenic variation, gametocyte transmission, bone marrow dysfunction, and loss of uninfected RBCs. New strategies and insights published by the Malaria Host-Pathogen Interaction Center (MaHPIC) are recapped here along with a vision that stresses the importance of educating future experts well trained in utilizing NHP infection model systems for the pursuit of innovative, effective interventions against malaria.

摘要

《灵长类疟原虫》一书自 1971 年首次出版以来,一直是多代科学家的独特重要资源,至今仍然与当今息息相关。事实上,50 多年来,非人类灵长类动物(NHPs)在疟疾的基础和临床前研究方面取得了重大突破,发挥了重要作用。涉及 NHPs 的研究提供了关键的见解和数据,这些对于许多寄生虫物种、药物、疫苗、发病机制和传播的疟疾研究至关重要,从而改善了临床护理,并推进了疟疾控制、消除和根除的研究目标。虽然几十年来大多数疟疾科学家一直在研究恶性疟原虫,通过 NHPs 感染,在人类临床研究中,或使用体外培养或啮齿动物模型系统,但其他人一直在致力于推进间日疟原虫以及与亲缘关系密切的灵长类物种的研究,包括食蟹猴疟原虫、库蚊疟原虫和疟原虫 knowlesi。多年来对这四个亲缘关系密切的物种的深入研究催生了设计 NHPs 纵向感染策略的灵感,用于收集有关正在进行的感染的信息,这些信息可以与人类感染有关。在这里,我们回顾了这些疟原虫与 NHPs 的感染模型系统,重点介绍了现代系统生物学方法在研究纵向感染、发病机制、免疫和疫苗方面的应用。最近利用 NHPs 纵向感染的发现包括对慢性感染、复发、贫血和免疫记忆的深入理解。随着快速出现的新技术进步,可以预期在这些和其他关键主题上进行更深入的研究和机制发现,包括休眠子生物学、抗原变异、配子体传播、骨髓功能障碍和未感染 RBC 的丧失。本文总结了疟疾宿主-病原体相互作用中心(MaHPIC)发表的新策略和新见解,并展望了未来的发展方向,强调了教育未来专家的重要性,让他们能够熟练地利用 NHPs 感染模型系统,追求针对疟疾的创新、有效的干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8e7/9175500/3e98410a5137/12936_2022_4199_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8e7/9175500/3e98410a5137/12936_2022_4199_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8e7/9175500/3e98410a5137/12936_2022_4199_Fig1_HTML.jpg

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本文引用的文献

[1]
A spatiotemporally resolved single-cell atlas of the Plasmodium liver stage.

Nature. 2022-11

[2]
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Front Cell Infect Microbiol. 2022

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Front Mol Biosci. 2022-2-15

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Antigen Discovery in Circulating Extracellular Vesicles From Patients.

Front Cell Infect Microbiol. 2021

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