COVID-19 Supplement: Systems Immune Profiling of Divergent Responses to Infection

人类免疫学项目联盟（HIPC）计划的总体目标是利用最近的 免疫分析方法的进展，以创造一种新的公共资源， 人体免疫系统的状态。我们建议通过深入的 询问和广泛的系统方法，将识别不同分子的分子特征 人体对感染的免疫反应构成我们U19的三个项目都利用了 共同的实验基础设施，重点放在不同的传染病：莱姆病 螺旋体伯氏疏螺旋体，新出现的节肢动物传播的西尼罗河病毒，以及衰老对 接种流感疫苗。我们的目标是描绘出人类免疫特征， 人群中的不同表现，使用定义明确的患者队列和多维 分析方法来定量评估原代人免疫细胞功能。我们的计划雇用 尖端的免疫分析，如CyTOF多维分析、代谢组学、纳米 技术，如MuSIC（多光谱成像细胞术）和RNA-seq的单细胞，将 告知系统方法来阐明定义免疫应答的生物特征。 不同组织和不同感染类型的反应之间的共性将是 通过量化签名富集，并通过识别保守的主动子网络， 免疫特异性功能网络。 这种合作U19利用我们机构的巨大优势， 人类免疫学中的挑战性问题。这项提案中的调查人员已经建立了合作关系， 定期的互动，以及分享成功的记录。我们的三个研究项目得到了 用于管理、数据管理和分析、单细胞免疫表型分析和 临床招募这些不同方法的统一目标是定义免疫的要素， 导致不同感染结果的反应。这种对免疫系统的多因素、宽视角的观点 将利用系统建模的每一种方法的专门知识， 对三组分层患者队列的深入询问。该功能系统的输出 免疫学方法将是在多种形式的感染性疾病之后的人类免疫特征的定义。 最终目标是确定未来的干预目标和预测易感性， 阻力

The overall goal of the Human Immunology Project Consortium (HIPC) program is to capitalize on recent advances in immune profiling methods in order to create a novel public resource that characterizes diverse states of the human immune system. We propose to contribute to this program through deep interrogation and a broad systems approach that will identify molecular signatures of divergent human immune responses to infections. The three projects that comprise our U19 each leverage a common experimental infrastructure to focus on a different infectious diseases: the Lyme disease spirochete Borrelia burgdorferi, emerging arthropod-borne West Nile virus, and effects of aging on vaccination against influenza. Our goal is to delineate human immune signatures that are associated with the divergent manifestations in the population, using well-defined patient cohorts and a multidimensional analytical approach to quantitatively assess primary human immune cell function. Our program employs cutting-edge immune profiling such as multidimensional profiling by CyTOF, metabolomics, nanoscale technologies such as MuSIC (MultiSpectral Imaging Cytometry), and RNA-seq on single cells that will inform a systems approach to elucidate the biologic signatures defining immune responsiveness. Commonalities between the responses in different tissues, and to the different infection types, will be determined by quantifying signature enrichments, and by identifying conserved active sub-networks in this immune-specific functional network. This collaborative U19 takes advantage of enormous strengths across our institutions to tackle a challenging issue in human immunology. The investigators in this proposal have established collaborations, regular interactions, and a track record of shared success. Our three research projects are supported by shared cores for Administration, Data Management and Analysis, Single Cell Immunophenotyping, and Clinical Recruitment. The united goal of these varied approaches is to define elements of the immune response that contribute to divergent infection outcomes. This multifactorial, wide-angle view of the immune response will be compiled employing the expertise of each individual approach for Systems Modeling from deep interrogation of three sets of stratified patient cohorts. The output of this functional systems immunology approach will be definitions of human immune signatures following multiple forms of infectious challenges with the ultimate goal of defining future targets for intervention and predicting susceptibility or resistance.