Centre for Respiratory Research, Department of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
PLoS One. 2011;6(10):e24581. doi: 10.1371/journal.pone.0024581. Epub 2011 Oct 13.
Immunity to infections caused by Streptococcus pneumoniae is dependent on complement. There are wide variations in sensitivity to complement between S. pneumoniae strains that could affect their ability to cause invasive infections. Although capsular serotype is one important factor causing differences in complement resistance between strains, there is also considerable other genetic variation between S. pneumoniae strains that may affect complement-mediated immunity. We have therefore investigated whether genetically distinct S. pneumoniae strains with the same capsular serotype vary in their sensitivity to complement mediated immunity.
C3b/iC3b deposition and neutrophil association were measured using flow cytometry assays for S. pneumoniae strains with different genetic backgrounds for each of eight capsular serotypes. For some capsular serotypes there was marked variation in C3b/iC3b deposition between different strains that was independent of capsule thickness and correlated closely to susceptibility to neutrophil association. C3b/iC3b deposition results also correlated weakly with the degree of IgG binding to each strain. However, the binding of C1q (the first component of the classical pathway) correlated more closely with C3b/iC3b deposition, and large differences remained in complement sensitivity between strains with the same capsular serotype in sera in which IgG had been cleaved with IdeS.
These data demonstrate that bacterial factors independent of the capsule and recognition by IgG have strong effects on the susceptibility of S. pneumoniae to complement, and could therefore potentially account for some of the differences in virulence between strains.
对肺炎链球菌引起的感染的免疫力依赖于补体。肺炎链球菌菌株之间对补体的敏感性存在广泛差异，这可能影响它们引起侵袭性感染的能力。虽然荚膜血清型是导致菌株间补体耐药性差异的一个重要因素，但肺炎链球菌菌株之间也存在相当大的其他遗传变异，这可能影响补体介导的免疫。因此，我们研究了具有相同荚膜血清型但遗传背景不同的肺炎链球菌菌株在对补体介导的免疫敏感性方面是否存在差异。
使用流式细胞术测定了具有不同遗传背景的 8 种荚膜血清型肺炎链球菌菌株对补体的 C3b/iC3b 沉积和中性粒细胞结合的敏感性。对于某些荚膜血清型，不同菌株之间的 C3b/iC3b 沉积存在明显差异，这与荚膜厚度无关，与对中性粒细胞结合的易感性密切相关。C3b/iC3b 沉积结果也与每种菌株与 IgG 的结合程度弱相关。然而，C1q（经典途径的第一个成分）的结合与 C3b/iC3b 沉积更密切相关，并且在 IdeS 切割 IgG 后，同一种荚膜血清型的菌株之间在补体敏感性方面仍然存在很大差异。
这些数据表明，细菌因子独立于荚膜和 IgG 的识别，对肺炎链球菌对补体的敏感性有很强的影响，因此可能是菌株间毒力差异的部分原因。
