Neutrophil extracellular trap formation in the Streptococcus suis infected cerebrospinal fluid compartment

猪链球菌感染脑脊液室中中性粒细胞胞外陷阱的形成

• 批准号: 320253943
• 负责人: Professor Dr. Christoph Baums
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/320253943?language=en
• 关键词: Neutrophil; extracellular; trap; formation; Streptococcus

Streptococcus (S.) suis is one of the most important pathogens in pigs and also an emerging zoonotic agent, causing meningitis and various other pathologies. The pathogenesis of S. suis infections is highly complex and still only poorly understood. Infiltrations with high numbers of neutrophils are typical for S. suis diseases. Neutrophil extracellular traps (NETs) are an important defence mechanism against different pathogens, but its role during S. suis infections and also during meningitis in general, has not been studied so far. Therefore, the goal of the proposed project is to explore the role of NETs in the pathogenesis of S. suis meningitis focussed on the cerebrospinal fluid compartment. Preliminary experiments revealed that S. suis can induce NET-formation in porcine and human blood-derived neutrophils. On the other hand, S. suis also exhibited the ability to evade entrapment by NETs using the DNases SsnA and EndAsuis to degrade NETs. Thus, this project is designed to investigate the role of NETs in the pathogenesis of S. suis meningitis. Human and porcine models of the blood-cerebrospinal fluid barrier as well as in vivo studies using the pig as natural host will be used to elucidate the impact of NET formation and NET degradation on the host cell-pathogen interaction in the cerebrospinal fluid compartment. The cooperation of both partners, C. Baums and M. von Köckritz-Blickwede, with their expertise in S. suis pathogenesis and NET formation, respectively, provides an excellent condition for the realization of this project.

链球菌（S.）猪流感是猪的最重要病原体之一，也是一种新出现的人畜共患病原体，可引起脑膜炎和各种其他疾病。对S.猪流感的感染非常复杂，而且仍然知之甚少。大量中性粒细胞浸润是典型的链球菌感染。猪的疾病。中性粒细胞胞外陷阱（NETs）是一种重要的防御机制，但它在S.猪传染病和一般脑膜炎期间，迄今尚未进行研究。因此，该项目的目标是探索NET在S.猪的脑膜炎集中在脑脊髓液室。初步实验表明，S.猪可以诱导猪和人血液来源的中性粒细胞中的NET形成。另一方面，S. suis还表现出使用DNA酶SsnA和EndAsuis降解NET来逃避NET的捕获的能力。因此，本课题旨在研究NETs在S.猪脑膜炎。人和猪的血液-脑脊液屏障模型以及使用猪作为天然宿主的体内研究将用于阐明NET形成和NET降解对脑脊液隔室中宿主细胞-病原体相互作用的影响。双方的合作，C。Baums和M. von Köckritz-Blickwede，凭借他们在S.猪的发病机理和NET的形成，为该项目的实现提供了良好的条件。