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Analysis of host defense system against pathogenic oral bacteria in oral epithelial cells by the intracellular PAMPs receptors

细胞内PAMPs受体分析口腔上皮细胞针对口腔致病菌的宿主防御系统

基本信息

批准号：
17591904
负责人：
NAKAGAWA Ichiro
金额：
$ 2.18万
依托单位：
Tokyo University (2006)Osaka University (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Macroautophagy(referred to as autophagy) is a unique form of membrane trafficking in which membrane compartments(autophagosome) engulf both organella and cytosolic macromolecules and deliver them to the lysosomes. Many pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. The endocytic degradation pathway is thought to be the only prevention against such intracellular pathogens. Autophagy, a fundamental cellular homeostasis pathway that operates with the intracellular degradation/recycling system, causes the turnover of cellular components by delivering portions of the cytoplasm and organelles to lysosomes. Recently, we reported that autophagic degradation is a previously unrecognized effector of host innate immunity. Streptococcus pyogenes(Group A Streptococcus ; GAS) successfully enters human epithelial cells via endocytosis. GAS immediately escapes from the endosomes to the cytoplasm and gains a replicative niche, after which GAS in the cytoplasm is trapped in autophagosome-like compartments and degraded upon fusion with lysosomes. This process indicates that autophagy plays a protective role in infectious diseases. We also found that autophagic degradation was induced against Staphylococcus aureus, while methicillin-resistant S.aureus were resistant to autophagic degradation. We also found some intracellular NLRP were related to the recognition of intracellular bacteria to induce autophagosome formation.

大自噬（macroautophagy）是一种独特的膜运输形式，其中膜隔室（自噬体）吞噬细胞器和细胞溶质大分子并将它们递送到溶酶体。许多病原菌可以侵入吞噬细胞和非吞噬细胞，并在细胞内定植，然后传播到其他细胞。内吞降解途径被认为是对这种细胞内病原体的唯一预防。自噬是一种基本的细胞内稳态途径，与细胞内降解/再循环系统一起运作，通过将部分细胞质和细胞器递送到溶酶体来引起细胞组分的周转。最近，我们报道了自噬降解是一种以前未被认识到的宿主先天免疫效应。化脓性链球菌（A组链球菌; GAS）通过内吞作用成功进入人上皮细胞。GAS立即从内体逃逸到细胞质并获得复制小生境，之后细胞质中的GAS被捕获在自噬体样隔室中并在与溶酶体融合时降解。这一过程表明，自噬在感染性疾病中起着保护作用。我们还发现，自噬降解诱导对金黄色葡萄球菌，而耐甲氧西林金黄色葡萄球菌耐自噬降解。我们还发现一些细胞内的NLRP与细胞内细菌的识别有关，从而诱导自噬体的形成。