HIPC U19 Project 1

重债穷国 U19 项目 1

• 批准号: 10598128
• 负责人: Matthew C. Altman
• 金额: $ 12.54万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-29 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598128
• 关键词: Acute; Adult; Allergens; Allergic; Antibodies; Antigens; Asthma; B-Cell Antigen Receptor; B-cell receptor repertoire sequencing; Blood specimen; CD8-Positive T-Lymphocytes; Cells; Child; Childhood; Chronic Disease; Clinical; Cytometry; DNA Methylation; Data; Data Analyses; Disease; Frequencies; Future; Gene Expression; Generations; Genetic; Genomics; Genotype; Goals; Hypersensitivity; IgE; Immune; Immune response; Immunity; Immunologic Memory; Immunology; Immunophenotyping; Infection; Inflammatory; Innate Immune Response; Intervention Studies; Kinetics; Lead; Ligands; Link; Lymphocyte; Measures; Membrane Proteins; Methods; Molecular; Morbidity - disease rate; Mucous Membrane; Nasal turbinate bone structure; Nature; Nose; Obesity; Outcome; Pathogenesis; Pathway interactions; Pattern; Phenotype; Population; Populations at Risk; Proteome; Receptor Cell; Reporting; Research; Resolution; Sampling; Seasons; Severities; Severity of illness; Source; Sputum; Standardization; Swab; Symptoms; System; Systems Biology; T-Lymphocyte; Time; Training; Viral; Viral Respiratory Tract Infection; Virus; Vulnerable Populations; acute infection; adaptive immune response; airway immune response; atopy; chronic respiratory disease; clinical phenotype; comorbidity; comparison control; data integration; demographics; disorder prevention; experience; high dimensionality; human disease; insight; molecular phenotype; mortality; multiple omics; novel; peripheral blood; programs; proteogenomics; pulmonary function; respiratory; respiratory infection virus; respiratory virus; response; sample collection; spatiotemporal; transcriptome

PROJECT SUMMARY/ABSTRACT – PROJECT 1 Acute respiratory viral infections (ARVI) are the most frequently occurring global illness producing significant morbidity and mortality, particularly in vulnerable populations. Children suffer higher frequencies of ARVI than adults and often experience re-infections. Common chronic diseases of childhood, most notably asthma but also allergies (atopy) and obesity, can predispose to increased severity of ARVI. The goal of Project 1 is to understand the longitudinal airway and systemic, innate and adaptive, immune responses to ARVI in vulnerable groups of children with asthma, atopy, and obesity compared to control children without these comorbidities. Furthermore, we will link these responses to clinical outcomes including infection duration and severity. Project 1 is highly synergistic with Project 2 and the Overall program by utilizing similar sample types, timing of sample collection, and common clinical endpoints; it differs by studying a distinct population of at-risk children and it includes disease specific assessments of allergic immune responses. Project 1 benefits from the overall program’s shared multi-omics approaches through a Genomics Core for the sample processing and generation of airway host transcriptome, proteome, DNA methylation, and viral quantity and expression data, along with host genetics. Similarly, it shares the Adaptive Phenotyping Core for the generation of high dimensional cytometry data to broadly characterize immune cell phenotypes and for detailed identification of antigen-specific cells. The first aim will determine differences in longitudinal respiratory innate immune profiles in children with and without asthma, atopy, and obesity in response to ARVI using multi-omic assessments of airway samples. The second aim will determine differences in short-term and long-term adaptive cellular responses including a detailed characterization of viral-specific and allergen-specific T cell populations. The third aim will utilize single cell gene expression, TCR/BCR sequencing, and surface protein quantification (TotalSeq) to provide cell specific granularity of both mucosal and systemic responses. This study will determine networks of airway and systemic immune pathways that lead to adaptive and maladaptive responses to ARVI in vulnerable children. Our research program will produce novel mechanistic insights into the diversity and commonality of immune responses to ARVI and use cutting-edge methods to provide novel insights for future studies of disease prevention and treatment.

项目摘要/摘要--项目1 急性呼吸道病毒感染(ARVI)是全球最常见的疾病， 发病率和死亡率，特别是在弱势群体中。儿童患ARVI的频率比 成人感染，经常会再次感染。儿童常见的慢性疾病，最明显的是哮喘，但 此外，过敏(特应性)和肥胖也容易导致ARVI严重程度的增加。项目1的目标是 了解ARVI的纵向气道和全身、先天和适应性免疫反应 患有哮喘、特应性疾病和肥胖的儿童的弱势群体与没有这些的对照儿童相比 合并症。此外，我们将把这些反应与临床结果联系起来，包括感染持续时间和 严肃性。通过利用相似的样本类型，项目1与项目2和整个方案具有高度的协同性， 样本收集的时间和常见的临床终点；它因研究不同的高危人群而有所不同 它包括对过敏性免疫反应的具体疾病评估。项目1受益于 整个计划的共享多组学方法通过基因组学核心进行样本处理和 生成呼吸道宿主转录组、蛋白质组、DNA甲基化以及病毒数量和表达数据， 以及宿主遗传学。同样，它共享用于产生High的自适应表型核心 用于广泛表征免疫细胞表型和详细鉴定免疫细胞表型的三维细胞术数据 抗原特异性细胞。第一个目标将确定纵向呼吸道天然免疫图谱的差异。 在有和没有哮喘、特应性和肥胖症的儿童中，使用多组学方法评估ARVI对其的反应 呼吸道样本。第二个目标将确定短期和长期适应细胞的差异。 反应包括病毒特异性和过敏原特异性T细胞群体的详细特征。这个 第三个目标将利用单细胞基因表达、TCR/BCR测序和表面蛋白定量 (TotalSeq)，以提供黏膜和全身反应的细胞特定粒度。这项研究将 确定导致适应性和适应性不良的呼吸道和系统免疫路径网络 弱势儿童对阿维菌素的反应。我们的研究计划将产生新的机械学见解 ARVI免疫应答的多样性和共性，并使用尖端方法提供新的 对未来疾病预防和治疗研究的见解。