Department of Neurology, Holtom-Garrett Program in Neuroimmunology, University of Michigan Medical School, Ann Arbor, MI 48109, United States.
J Neuroimmunol. 2010 Jan 25;218(1-2):83-93. doi: 10.1016/j.jneuroim.2009.10.006. Epub 2009 Nov 10.
Brain abscesses are mainly caused by either direct or indirect inoculation of gram positive bacteria including Stapylococcus aureus (S. aureus) or Streptococcus species into the central nervous system. In the present study, we aimed to compare potential changes in brain abscess pathogenesis induced by two different strains of S. aureus, namely the laboratory strain RN6390 and the clinical isolate Reynolds. Although the Reynolds strain was expected to be more resistant to eradication by the host, due to the existence of a polysaccharide capsule, and subsequently to be more virulent, instead we found parenchymal damage and mortality rates to be more prominent following RN6390 infection. In contrast, the Reynolds strain proliferated faster and induced early expression of the chemokine CXCL2, matrix metalloproteinase-9 (MMP-9), and complement 3a and C5. Furthermore, there were early and more abundant infiltration of PMNs, T cells and erythrocyte extravasation in brain abscesses induced by the Reynolds strain. However, several immune parameters were not different between the two strains during the later stages of the disease. These results suggest that capsular S. aureus can modulate innate immunity and complement system activation differently than the acapsular strain RN6390, and the early changes induced by Reynolds strain may have an important impact on survival.
脑脓肿主要由革兰氏阳性菌(包括金黄色葡萄球菌[S. aureus]或链球菌属)直接或间接接种到中枢神经系统引起。在本研究中,我们旨在比较两种不同金黄色葡萄球菌菌株(即实验室菌株 RN6390 和临床分离株 Reynolds)引起的脑脓肿发病机制的潜在变化。尽管预计 Reynolds 菌株由于存在多糖荚膜而更能抵抗宿主的清除,并且因此更具毒性,但我们发现,与 RN6390 感染相比,Reynolds 菌株感染后实质损伤和死亡率更为明显。相比之下,Reynolds 菌株增殖更快,并诱导趋化因子 CXCL2、基质金属蛋白酶-9(MMP-9)和补体 3a 和 C5 的早期表达。此外,Reynolds 菌株引起的脑脓肿中,PMN、T 细胞和红细胞渗出的早期和更丰富。然而,在疾病的后期阶段,两种菌株之间的几个免疫参数没有差异。这些结果表明,荚膜金黄色葡萄球菌可以与无荚膜菌株 RN6390 不同地调节先天免疫和补体系统激活,而 Reynolds 菌株诱导的早期变化可能对生存有重要影响。