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

链球菌(S.)猪瘟是猪最重要的病原体之一，也是一种新出现的人畜共患病病原体，可引起脑膜炎等多种疾病。猪链球菌感染的发病机制非常复杂，目前仍知之甚少。猪链球菌病的典型表现是大量中性粒细胞渗入。中性粒细胞胞外陷阱(Nets)是抵抗不同病原体的重要防御机制，但其在猪链球菌感染和一般脑膜炎中的作用尚未被研究。因此，该项目的目标是探索Nets在猪链球菌脑膜炎发病机制中的作用，主要集中在脑脊液室。初步实验表明，猪链球菌能诱导猪和人血源性中性粒细胞网状形成。另一方面，猪链霉菌也表现出利用DNA酶SsnA和EndAsuis来降解Net来躲避Net的诱捕的能力。因此，本项目旨在研究Nets在猪链球菌脑膜炎发病机制中的作用。将利用人和猪的血-脑脊液屏障模型以及以猪为自然宿主的体内研究来阐明网络的形成和网络的降解对脑脊液隔室中宿主细胞-病原体相互作用的影响。鲍姆斯和布利克韦德这两个分别在猪链球菌致病和网络形成方面的专业知识的合作伙伴为这一项目的实现提供了极好的条件。

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.