Role of NOD-like receptors in innate immune recognition of pathogenic bacteria

先天免疫系统装备有一系列细胞受体，它们迅速检测入侵的微生物并启动宿主防御。十年前，细胞内NOD样受体（NLR）被认为是先天免疫的重要组成部分。它们在抗微生物宿主防御中的作用是深入研究的主题，但目前对其特定功能的了解有限。在过去的6年里，我的NSERC资助的研究主要集中在对病原菌铜绿假单胞菌的先天免疫反应的分子机制。我的研究旨在了解这种微生物如何逃避免疫反应，导致严重感染。我假设NLR能够激活对铜绿假单胞菌的免疫反应，但随着细菌在宿主-病原体相互作用过程中发生突变并失去一些毒力因子，它们逃脱了NLR的识别，随后克服了宿主的防御。本研究的主要目的是探讨NLR在铜绿假单胞菌天然免疫和炎症反应中的作用。 我将回答以下具体问题：

The innate immune system is armed with an array of cellular receptors, which rapidly detect invading microorganisms and initiate host defense. Ten years ago, the intracellular NOD-like receptors (NLR) were recognized as an essential part of innate immunity. Their role in antimicrobial host defence is the subject of intensive research, but current knowledge on their specific functions is limited. During the last 6 years, my NSERC-funded research has focused on molecular mechanisms involved in innate immune responses to pathogenic bacteria Pseudomonas aeruginosa. My research aims to understand how this microorganism escapes immune responses resulting in severe infections. I hypothesize that NLRs are able to activate immune responses to P. aeruginosa, but as bacteria undergo mutations and lose some virulence factors in the process of host-pathogen interactions, they escape recognition by NLRs and subsequently overcome host defenses. The major objective of my proposed research program: to investigate the involvement of NLRs in innate immune and inflammatory responses to P. aeruginosa. I will address the following specific questions: