MICROBES, DENDRITIC CELL SUBSETS AND T-CELL IMMUNITY

微生物、树突状细胞亚群和 T 细胞免疫

• 批准号: 7715694
• 负责人: BALI PULENDRAN
• 金额: $ 3.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715694
• 关键词: CD4 Positive T Lymphocytes; Cells; Class; Clinical; Computer Retrieval of Information on Scientific Projects Database; Dendritic Cells; Drosophila genus; Escherichia coli; Funding; Grant; Helminths; Helper-Inducer T-Lymphocyte; IgE; Immune response; Immune system; Immunity; Infection; Institution; Interleukin-10; Interleukin-4; Interleukin-5; Mediating; Microbe; Ovalbumin; Pattern recognition receptor; Porphyromonas gingivalis; Proteins; Research; Research Personnel; Resources; Signal Transduction; Signaling Molecule; Source; TLR4 gene; Th1 Cells; Th2 Cells; United States National Institutes of Health; cytokine; eosinophil; novel; novel strategies; pathogen; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The adaptive immune system has evolved several different lines of attack, each one optimally effective against a given pathogen. For example, in response to intracellular microbes, CD4+ T-helper cells (Th) differentiate into Th1 cells; in contrast helminths induce Th2 cells, whose cytokines (IL-4, IL-5 & IL-10) induce IgE and eosinophil-mediated destruction of the pathogens. Although these diverse responses have been characterized in detail, the mechanism by which a particular type of immune response is initiated is poorly understood. Analogous to the situation in Drosophila, signaling through distinct TLRs can yield qualitatively different immune responses. Furthermore, we suggest that different DC subsets are endowed with a distinct, repertoires of pattern recognition receptors, which enable them to recognize distinct classes of pathogens, and initiate different types of immune responses. In this proposal, we will co-inject a soluble protein (ovalbumin) with either of two different LPs molecules that signal through distinct pattern recognition receptors : (i) E. coli LPS, which signals through TLR4, and induces Th1 cytokines, and (ii) P. gingivalis LPS, which signals independently of TLR4. P. gingivalis infections are often characterized by Th2 cytokines. This research provides a novel mechanism by which distinct pathogens can elicit distinct adaptive immunity, by targeting different cells of the innate immune system. Such results offer novel strategies for manipulating immune responses in clinical settings.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 自适应免疫系统已经进化出了几种不同的攻击线，每种攻击线都针对给定的病原体有效。例如，为了响应细胞内微生物，CD4+ T-辅助细胞（Th）分化为Th1细胞。相反，蠕虫诱导Th2细胞，其细胞因子（IL-4，IL-5和IL-10）诱导病原体的IgE和嗜酸性粒细胞介导的破坏。尽管这些不同的反应已详细介绍了这些不同的反应，但启动特定类型的免疫反应的机制知之甚少。 类似于果蝇的情况，通过不同的TLR发出信号可以产生质量不同的免疫反应。此外，我们建议不同的DC子集赋予模式识别受体的独特曲目，这使他们能够识别不同类型的病原体，并启动不同类型的免疫反应。在此提案中，我们将与两个不同的LPS分子中的任何一个一起注入可溶性蛋白（卵巢蛋白），它们通过不同的模式识别受体发出信号：（i）通过TLR4发出信号的E. coli LPS，并诱导Th1细胞因子和（II）P。gingivalis LPS，其中具有独立于TLR4的信号。牙龈疟原虫感染通常以Th2细胞因子为特征。 这项研究提供了一种新的机制，通过靶向先天免疫系统的不同细胞，可以通过这种机制来引起不同的适应性免疫。这样的结果为操纵临床环境中的免疫反应提供了新的策略。