Yau Belinda, Too Lay Khoon, Ball Helen J, Hunt Nicholas H
Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.
Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.
Microbes Infect. 2017 Jul-Aug;19(7-8):413-421. doi: 10.1016/j.micinf.2017.04.002. Epub 2017 Apr 22.
Streptococcus pneumoniae (S. pneumoniae) meningitis causes debilitating neurological symptoms and acute fatalities in patients, and long-term neurological sequelae in some survivors. Current vaccines do not protect against all 94 known S. pneumoniae capsular serotypes, many of which are capable of causing pneumococcal meningitis (PM). We here compare the pathogenic outcomes of two clinically virulent isolates of S. pneumoniae, serotype 3 strain WU2 and serotype 4 strain TIGR4, in a murine model of PM. At an identical infectious dosage of 10 CFU administered via the intracerebroventricular route, significantly greater mortality, interleukin (IL)1β and IL6 production, and blood-brain barrier dysfunction occurred in TIGR4-induced PM compared to PM caused by WU2. Higher bacterial counts in the cerebrospinal fluid and nitrite/nitrate in serum were observed 40 h post inoculation with TIGR4 compared to mice infected with WU2. Similar to our previous findings in WU2 PM, interferon-γ was an essential driver of the pathogenesis of TIGR4 PM, suggesting that this cytokine may be a common pathogenic agent across a range of pneumococcal meningitides and, thus, a potential therapeutic target for intervention.
肺炎链球菌脑膜炎可导致患者出现使人衰弱的神经症状和急性死亡，部分幸存者还会出现长期神经后遗症。目前的疫苗不能预防所有94种已知的肺炎链球菌荚膜血清型，其中许多血清型都可引发肺炎球菌脑膜炎（PM）。我们在此比较了两种具有临床致病性的肺炎链球菌分离株，即3型菌株WU2和4型菌株TIGR4，在PM小鼠模型中的致病结果。通过脑室内途径给予相同的10 CFU感染剂量时，与WU2引起的PM相比，TIGR4引起的PM死亡率显著更高，白细胞介素（IL）-1β和IL-6产生更多，血脑屏障功能障碍更严重。接种TIGR4后40小时，与感染WU2的小鼠相比，观察到脑脊液中的细菌计数更高，血清中的亚硝酸盐/硝酸盐含量更高。与我们之前在WU2引起的PM中的发现相似，干扰素-γ是TIGR4引起的PM发病机制的关键驱动因素，这表明这种细胞因子可能是多种肺炎球菌脑膜炎的常见致病因子，因此可能是干预的潜在治疗靶点。
