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 免疫图谱方法的进展，以创建具有多样性特征的新型公共资源 人类免疫系统的状态。我们建议通过深水为这一项目做出贡献 讯问和广泛的系统方法，将确定分歧的分子特征 人类对感染的免疫反应。组成我们U19的三个项目每个都利用了 共同的实验基础设施专注于一种不同的传染病：莱姆病 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信号与 人群中的不同表现，使用定义明确的患者队列和多维的 定量评估原代人体免疫细胞功能的分析方法。我们的计划雇佣了 前沿免疫图谱，如细胞多维图谱、代谢组学、纳米尺度 单细胞上的MUSIC(多光谱成像细胞术)和RNA-SEQ等技术将 告知系统方法，以阐明定义免疫反应性的生物特征。 不同组织和不同感染类型的反应之间的共性将是 通过量化签名丰富并通过识别此中保守的活动子网络来确定 免疫专一性功能网络。 这款协作式U19利用我们各机构的巨大优势， 人类免疫学中具有挑战性的问题。这项提案中的调查人员已经建立了合作关系， 定期互动，以及共同成功的记录。我们的三个研究项目得到了 用于管理、数据管理和分析、单细胞免疫表型鉴定以及 临床招募。这些不同方法的共同目标是定义免疫的要素 导致不同感染结果的反应。这种多因素、广角的免疫观点 将使用每种单独的系统建模方法的专业知识来编制响应 深度询问三组分层患者队列。这个功能系统的输出 免疫学方法将在多种形式的传染性疾病之后定义人类免疫特征 挑战的最终目标是定义未来的干预目标和预测易感性 抵抗。

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.