Autophagy as a component of the innate immune response

自噬作为先天免疫反应的一个组成部分

• 批准号: 7689597
• 负责人: MICHELE Somes SWANSON
• 金额: $ 37.77万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7689597
• 关键词: Alveolar Macrophages; Amino Acids; Autophagocytosis; Autophagosome; Bacteria; Biological Assay; C57BL/6 Mouse; Caspase-1; Cell Death; Commit; Complex; Cytolysis; Cytoplasm; Data; Development; Dose; Enzyme-Linked Immunosorbent Assay; Epitopes; Flagellin; Fluorescence Microscopy; Genetic; Human; Immune response; Immune system; Infection; Inflammatory; Interleukin-18; Knowledge; Legionella pneumophila; Leukocytes; Life; Lung; Lysosomes; Mammalian Cell; Microbe; Microscopy; Molecular; Mus; Natural Immunity; Nutrient; Pathway interactions; Pattern; Proteins; Rate; Route; Signal Transduction; Starvation; Testing; Toll-like receptors; Virulence; Virulent; Withdrawal; abstracting; deprivation; macrophage; microbial; mutant; particle; pathogen; respiratory; response; tool; trait

Abstract An exciting development in the innate immunity field is the discovery that macrophages enlist autophagy to protect their cytoplasm from infection. Nutrient deprivation has long been known to induce autophagy, but how infection rapidly triggers this alternate route to digestive lysosomes is poorly understood. Genetic data indicate that mice resist L. pneumophila infection by relying on NOD-like proteins to detect cytosolic flagellin and then to digest the microbes by autophagy or to commit a pro-inflammatory cell death known as pyroptosis. To determine how macrophages integrate autophagy and pyroptosis as barriers to microbial infection, we will exploit Legionella pneumophila as a genetic probe of the innate immune system.

摘要 先天免疫领域的一个令人兴奋的发展是发现巨噬细胞 利用自噬来保护细胞质免受感染长期以来， 已知会诱导自噬，但感染如何快速触发这种替代途径， 对消化溶酶体了解甚少。遗传学数据表明，小鼠抵抗L。 通过依赖NOD样蛋白来检测细胞溶质鞭毛蛋白， 然后通过自噬来消化微生物， 也就是焦亡为了确定巨噬细胞如何整合自噬和 作为微生物感染的屏障，我们将利用嗜肺军团菌作为 先天免疫系统的基因探针