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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.

恶性疟原虫是造成2亿多临床疟疾病例和50万人死亡的原因每年恶性疟疾对生活在流行区的幼儿造成伤害逐渐获得对疾病的免疫力尽管获得性免疫对疟疾很重要，但我们仍然对这个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收集的血液样本，宿主和寄生虫基因表达在获得抗恶性疟免疫中的作用。一是比较转录组反应的第一个恶性疟原虫感染的儿童，然后保持免费的症状持续五年，与那些发生多次临床疟疾发作的匹配儿童的症状相似。第二、我们将分析发生在同一个孩子身上的基因表达的变化，为了更好地理解伴随免疫力逐渐获得的分子变化。总的来说，我们的研究将提供一个独特的视角，在寄生虫和宿主基因表达的作用，获得抗临床疟疾的免疫力，并可提供指导开发的重要信息更有效的疟疾疫苗。