Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Int J Mol Sci. 2020 Jul 25;21(15):5289. doi: 10.3390/ijms21155289.
is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigated the role of the secreted nuclease A of (SsnA) as a NET-evasion factor in vivo and in vitro. Piglets were intranasally infected with strain 10 or an isogenic mutant. DNase and NET-formation were analyzed in cerebrospinal fluid (CSF) and brain tissue. Animals infected with strain 10 or S. suis 10ΔssnA showed the presence of NETs in CSF and developed similar clinical signs. Therefore, SsnA does not seem to be a crucial virulence factor that contributes to the development of meningitis in pigs. Importantly, DNase activity was detectable in the CSF of both infection groups, indicating that host nucleases, in contrast to bacterial nuclease SsnA, may play a major role during the onset of meningitis. The effect of DNase 1 on neutrophil functions was further analyzed in a 3D-cell culture model of the porcine blood-CSF barrier. We found that DNase 1 partially contributes to enhanced killing of by neutrophils, especially when plasma is present. In summary, host nucleases may partially contribute to efficient innate immune response in the CSF.
是一种引起猪和人类脑膜炎的人畜共患病原体。中性粒细胞作为抵御感染的第一道防线，会释放中性粒细胞胞外诱捕网（NETs）来捕获病原体。在这项研究中，我们研究了分泌的核酸酶 A（SsnA）作为一种 NET 逃避因子在体内和体外的作用。猪只通过鼻腔感染 10 号菌株或同源的 突变株。在脑脊液（CSF）和脑组织中分析了 DNA 酶和 NET 形成。感染 10 号菌株或 S. suis 10ΔssnA 的动物在 CSF 中存在 NET，并表现出相似的临床症状。因此，SsnA 似乎不是导致猪脑膜炎发展的关键毒力因子。重要的是，在这两个感染组的 CSF 中均可检测到 DNA 酶活性，表明宿主核酸酶可能与细菌核酸酶 SsnA 相反，在脑膜炎发病过程中发挥主要作用。在猪血液-CSF 屏障的 3D 细胞培养模型中进一步分析了 DNA 酶 1 对中性粒细胞功能的影响。我们发现 DNA 酶 1 部分有助于增强中性粒细胞对 的杀伤作用，尤其是在存在血浆时。总之，宿主核酸酶可能部分有助于 CSF 中有效的先天免疫反应。
