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Mechanisms of host adaptation and immune evasion of Neisseria meningitidis: the role of biofilms and blebs

脑膜炎奈瑟菌的宿主适应和免疫逃避机制：生物膜和泡的作用

基本信息

批准号：
210847372
负责人：
Professor Dr. Ulrich Vogel
金额：
--
依托单位：
Institut für Hygiene und Mikrobiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/210847372?language=en
关键词：
Mechanisms host adaptation immune evasion

项目摘要

Neisseria meningitidis colonizes the human nasopharynx and sporadically causes severe invasive disease in childhood and adolescence. In the past decades, a variety of molecular mechanisms have been elucidated that are employed by meningococci for host adaptation and immune evasion. In this application, we will investigate the role of biofilms and outer membrane vesicles as previously neglected morphological structures possibly involved in pathogen host interaction and immune evasion. Based on our published work on biofilms, we will study biofilm detachment processes, which we think are essential for within-host spread and between-host transmission. We will focus on the investigation of dynamic expression of the pilus apparatus. Furthermore, we will test the hypothesis that the detachment phase differs in the so-called settler and spreader strains, which we recently proposed as two basic lifestyles of meningococci. In preparatory work we recently collected convincing evidence that meningococcal outer membrane vesicles interfere with neutrophil effector mechanisms. We will therefore study the molecular mechanisms behind the effect of outer membrane blebs on immune evasion strategies. Bleb mediated avoidance of serum complement attack, silencing of neutrophils, and escape of neutrophil extracellular traps by bleb release will be focus of the investigations.

脑膜炎奈瑟菌在人类鼻咽部定植，在儿童和青春期偶尔会引起严重的侵袭性疾病。在过去的几十年里，脑膜炎球菌用于宿主适应和免疫逃避的各种分子机制已经被阐明。在这一应用中，我们将研究生物膜和外膜囊泡作为以前被忽视的形态结构的作用，这些结构可能涉及病原体与宿主的相互作用和免疫逃避。基于我们已发表的关于生物膜的工作，我们将研究生物膜的分离过程，我们认为这是宿主内传播和宿主间传播所必需的。我们将重点研究毛膜器的动态表达。此外，我们将检验我们最近提出的脑膜炎双球菌的两种基本生活方式，即分离阶段在所谓的迁移型和传播型菌株中不同的假设。在准备工作中，我们最近收集了令人信服的证据，证明脑膜炎双球菌外膜小泡干扰了中性粒细胞效应机制。因此，我们将研究外膜小泡对免疫逃避策略的影响背后的分子机制。BLOB介导的避免血清补体攻击、抑制中性粒细胞以及通过释放BLOB逃逸中性粒细胞胞外陷阱将是研究的重点。