Reactive oxygen species as modulators and effectors of epithelial defense: A role for NOD-like receptors?

活性氧作为上皮防御的调节剂和效应物：NOD 样受体的作用？

• 批准号: 173485877
• 负责人: Professor Dr. Philip Caspar Rosenstiel, Ph.D.
• 金额: --
• 依托单位: Institut für Klinische Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/173485877?language=en
• 关键词: Reactive; oxygen; species; modulators; effectors

Generation of microbicidal reactive oxygen species (ROS) is a pivotal protective component of the innate immune system in many eukaryotes. NOD (nucleotide oligomerisation domain containing protein)-like receptors (NLRs) have been implicated as phylogenetically ancient sensors of intracellular pathogens or endogenous danger signals. NOD2 recognizes the bacterial cell wall component muramyldipeptide (MDP) leading to NF-κB and MAPK activation via induced proximity signaling through the serine threonine kinase RIP2. In addition to the subsequent induction of cytokines and antimicrobial peptides, NOD2 has been shown to exert a direct antibacterial effect. Evidence points to a decisive role of NLRs as molecular switches involved both in the initiation and sensing of ROS production. Although the oxidative burst is well characterized as a defense tool of human neutrophils, very little is known about the role of redox homeostasis as an epithelial defense mechanism. The main goals of the project will be to investigate the link between cellular redox homeostasis and NLR signaling as a conserved antibacterial effector pathway and modulating principle of innate immunity signaling in the context of intestinal barrier function.

在许多真核生物中，产生杀微生物活性氧（ROS）是先天免疫系统的关键保护成分。NOD（核苷酸寡聚结构域含蛋白）样受体（NLRs）被认为是细胞内病原体或内源性危险信号的系统发育上的古老传感器。NOD2识别细菌细胞壁成分muramyldipeptide (MDP)，通过丝氨酸苏氨酸激酶RIP2诱导邻近信号通路激活NF-κB和MAPK。除了随后诱导细胞因子和抗菌肽外，NOD2已被证明具有直接的抗菌作用。有证据表明，nlr作为分子开关在ROS产生的启动和感知中都起着决定性作用。虽然氧化爆发被认为是人类中性粒细胞的防御工具，但对于氧化还原稳态作为上皮防御机制的作用知之甚少。该项目的主要目标将是研究细胞氧化还原稳态与NLR信号作为一种保守的抗菌效应途径之间的联系，以及肠道屏障功能背景下先天免疫信号的调节原理。

项目成果

RNAi screening identifies mediators of NOD2 signaling: Implications for spatial specificity of MDP recognition

• DOI: 10.1073/pnas.1209673109
• 发表时间: 2012-12-26
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Lipinski, Simone;Grabe, Nils;Rosenstiel, Philip
• 通讯作者: Rosenstiel, Philip

Nod2 is essential for temporal development of intestinal microbial communities

• DOI: 10.1136/gut.2010.216259
• 发表时间: 2011-10-01
• 期刊: GUT
• 影响因子: 24.5
• 作者: Rehman, Ateequr;Sina, Christian;Rosenstiel, Philip
• 通讯作者: Rosenstiel, Philip