Generation of a comprehensive panel of reagents for research on scavenger recepto

先天免疫系统是宿主防御的协作网络，它利用可溶性成分和 细胞防御。模式识别受体(PRRs)是先天免疫识别的核心，它识别 病原体衍生物或自身改变的成分通常不存在于健康宿主中。数量众多的家庭 PRRs已被发现，包括定义明确的Toll样受体和NOD样受体(TLR和NLR)。在……里面 除了这些分子，另一个PRR大家族是清道夫受体蛋白家族。 清道夫受体(SRS)是结构无关的受体，具有与多阴离子配体结合的能力。 这个简单的定义掩盖了SRs的重要性，因为PRRs-SRs是典型的多功能受体，通常 既能结合病原体的配体，又能结合自身的配体。在巡视潜在入口的细胞上发现SRs 病原体进入，如内皮细胞和吞噬细胞，包括巨噬细胞、树突状细胞和小胶质细胞。 不同的小区表达不同的PRR曲目，包括为它们提供唯一的PRR签名的SR， 由细胞类型和组织构成。除了作为吞噬细胞/内吞细胞 受体，一些SRs既独立地扫描信号，也与其他PRR家族合作扫描信号 TLRs对病原体做出反应。因此，通过组合信号，SRShelp微调病原体特异性 回应。此外，SRs是修饰的内源性配体的主要受体类别，提供了一种连接 先天免疫激活和无菌炎症性疾病之间的关系。然而，尽管SRIN很重要 病原体识别和这些分子在炎症、清道夫领域中新角色的出现 受体生物学明显落后于TLRs和NLRs。具体地说，几种基本试剂 由于缺乏对SRs的研究，因此限制了对其中许多分子的体外和体内研究。 在这里，我们建议重点开发基于清道夫受体的试剂。具体地说，我们建议开发 1)将促进SR生物学和SR-配体相互作用研究的试剂，2)抑制SRsin功能的试剂 配体摄取和信号传递以及3)将利用不同免疫细胞表达的SR来传递 基于纳米颗粒的试剂，用于体内特定的细胞亚群。 相关性(请参阅说明)： 对病原体的免疫防御是在微生物被模式识别受体识别后启动的。 清道夫受体(Sr)是这类受体中的一个重要家族，参与对多种细胞的保护作用。 病原体。了解SRS在免疫中的作用对于推进疫苗开发和 为生物防御和新出现的传染病创造新的治疗方法。我们建议生成一个 促进对这些重要的先天性免疫受体的研究的全面试剂小组

The innate immune system is a cooperative network of host defenses that utilizes both soluble components and cellular defenses. Central to innate immunerecognition are pattern recognition receptors (PRRs)that recognize pathogen derivatives or altered-self components normallyabsent from the healthy host. Numerousfamilies of PRRs have been identified includingthe well-defined Toll-likeand Nod-like receptors (TLRand NLRs). In addition to these molecules another large family of PRRs are the scavenger receptor family of proteins. Scavenger receptors (SRs) are structurally unrelated receptors that share the ability to bind polyanionic ligands. This simple definition belies the importance of SRsas PRRs - SRsare archetypal multifunctional receptors, often able to bind ligands of both pathogen and self-origin. SRsare found on cells that patrol potential portals of pathogen entry such as endothelial cells and phagocytes, including macrophages, dendriticcells andmicroglia. Different cells express distinct repertoires of PRRincludingSRsprovidingthem with a unique PRR signature, defined by both the cell type and the tissue oforigin. In addition to functioning as phagocytic/endocytic receptors, some SRscan both signal independently and cooperatively with other families of PRRs such as the TLRs to respond to pathogens. Thus, through combinatorialsignaling,SRshelp fine-tunepathogen-specific responses. In addition, SRsare the major class of receptors for modified endogenous ligands providinga link between innate immune activation and sterile inflammatorydiseases. However, despite the importance of SRsin pathogen recognition and the emergence of new roles for these molecules in inflammation, the field of scavenger receptor biologyhas significantly lagged behind that of TLRs and NLRs. Specifically, several essential reagents to study SRsare lackingand hence have limited the study of many of these molecules both in vitro and in vivo. Here we propose to focus on developing scavenger-receptor based reagents. Specifically we propose to develop reagents that 1) will facilitate studies of SRbiology and SR-ligand interactions, 2) inhibitthe function of SRsin ligand uptake and signalingand 3) that will utilizethe SRsexpressed by different immune cells to deliver nanoparticle based reagents to specific subpopulations of cells in vivo. RELEVANCE (See instructions): Immune defense against pathogens is initiated after microbial recognition by pattern recognition receptors. Scavenger receptors (SRs) are an important family of such receptors, involved in protection against diverse pathogens. Understanding the role of SRs in immunity is crucial to advance vaccine development and to generate new therapeutics for biodefense and emerging infectious diseases. We propose to generate a comprehensive panel of reagents to facilitate study of these important innate immune receptors