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Host and Parasite Transcriptional Changes Associated with Immunity to Clinical Malaria in Malian Children

与马里儿童临床疟疾免疫相关的宿主和寄生虫转录变化

基本信息

批准号：
9812115
负责人：
David Serre
金额：
$ 23.18万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-11 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9812115
关键词：
Affect Alleles Area Blood specimen Cessation of life Child Childhood Clinical Complement Data Development Disease Enrollment Expression Profiling Falciparum Malaria Gene Expression Gene Expression Profiling Gene Expression Regulation Genes Genetic Transcription Human Immune response Immunity Individual Infection Intervention Leukocytes Longitudinal Studies Longitudinal cohort study Malaria Malaria Vaccines Mali Molecular Parasites Pathway interactions Plasmodium falciparum Population Process Prophylactic treatment Research Design Risk Role Sampling Symptoms Testing Time Transcriptional Regulation Vaccines Variant acquired immunity base differential expression global health high risk population in vivo insight malaria infection novel programs response sample collection transcriptome sequencing transcriptomics transmission process vaccine development

项目摘要

Plasmodium falciparum is responsible for more than 200 million cases of clinical malaria and half a million deaths every year. Falciparum malaria disproportionally affects young children as individuals living in endemic areas gradually acquire immunity against the disease. Despite the importance of acquired immunity to malaria, we still know very little about the molecular and cellular bases of this dynamic process. Here, we propose to analyze blood samples collected during a five-year longitudinal study in Mali to comprehensively characterize the role of the host and parasite gene expression in the acquisition of immunity against falciparum malaria. First, we will compare the transcriptomic responses to a first P. falciparum infection of children who then remain free of symptoms for five years, to those of matched children who developed many clinical malaria episodes. Second, we will analyze the changes in gene expression occurring, in the same children, over five successive malaria episodes to better understand the molecular changes accompanying the gradual acquisition of immunity. Overall, our studies will provide a unique perspective on the role of the parasite and host gene expression in the acquisition of immunity against clinical malaria and could provide important information to guide the development of more efficient malaria vaccines.

恶性疟原虫造成2亿多例临床疟疾病例和50万人死亡每年都有。恶性疟疾作为流行地区的个体，对幼儿的影响不成比例。逐渐获得对疾病的免疫力。尽管对疟疾的后天免疫力很重要，但我们仍然对这一动态过程的分子和细胞基础知之甚少。在这里，我们建议分析在马里进行的一项为期五年的纵向研究期间采集的血液样本，以全面表征宿主和寄生虫基因在获得抗恶性疟疾免疫中的表达。首先，我们将比较未感染恶性疟原虫的儿童对首次感染恶性疟原虫的转录反应与出现多次临床疟疾发作的匹配儿童相比，这些儿童的症状持续了五年。第二, 我们将分析在相同的儿童中，在五次连续的疟疾中发生的基因表达的变化以更好地了解伴随免疫逐渐获得的分子变化。总的来说，我们的研究将为寄生虫和宿主基因的表达提供一个独特的视角获得对临床疟疾的免疫力，并可提供指导发展的重要信息更有效的疟疾疫苗。