Centre for Respiratory Research, Department of Medicine, University College Medical School, Rayne Institute, 5 University Street, London WC1E 6JJ, United Kingdom.
Infect Immun. 2010 Feb;78(2):716-25. doi: 10.1128/IAI.01056-09. Epub 2009 Nov 30.
Streptococcus pneumoniae strains vary considerably in the ability to cause invasive disease in humans, and this is partially associated with the capsular serotype. The S. pneumoniae capsule inhibits complement- and phagocyte-mediated immunity, and differences between serotypes in these effects on host immunity may cause some of the variation in virulence between strains. However, the considerable genetic differences between S. pneumoniae strains independent of the capsular serotype prevent an unambiguous assessment of the effects of the capsular serotype on immunity using clinical isolates. We have therefore used capsular serotype-switched TIGR4 mutant strains to investigate the effects of the capsular serotype on S. pneumoniae interactions with complement. Flow cytometry assays demonstrated large differences in C3b/iC3b deposition on opaque-phase variants of TIGR4(-)+4, +6A, +7F, and +23F strains even though the thicknesses of the capsule layers were similar. There was increased C3b/iC3b deposition on TIGR4(-)+6A and +23F strains compared to +7F and +4 strains, and these differences persisted even in serum depleted of immunoglobulin G. Neutrophil phagocytosis of the TIGR4(-)+6A and +23F strains was also increased, but only in the presence of complement, showing that the effects of the capsular serotype on C3b/iC3b deposition are functionally significant. In addition, the virulence of the TIGR4(-)+6A and +23F strains was reduced in a mouse model of sepsis. These data demonstrate that resistance to complement-mediated immunity can vary with the capsular serotype independently of antibody and of other genetic differences between strains. This might be one mechanism by which the capsular serotype can affect the relative invasiveness of different S. pneumoniae strains.
肺炎链球菌菌株在引起人类侵袭性疾病的能力上有很大差异，这部分与荚膜血清型有关。肺炎链球菌荚膜抑制补体和吞噬细胞介导的免疫，血清型之间在这些对宿主免疫的影响上的差异可能导致菌株间毒力的一些变化。然而，肺炎链球菌菌株之间除荚膜血清型之外的遗传差异很大，这使得使用临床分离株来明确评估荚膜血清型对免疫的影响变得不可能。因此，我们使用荚膜血清型转换的 TIGR4 突变株来研究荚膜血清型对肺炎链球菌与补体相互作用的影响。流式细胞术分析表明，即使荚膜层的厚度相似，TIGR4(-)+4、+6A、+7F 和 +23F 菌株的不透明相变体上 C3b/iC3b 的沉积也有很大差异。与 +7F 和 +4 菌株相比，TIGR4(-)+6A 和 +23F 菌株上的 C3b/iC3b 沉积增加，即使在缺乏 IgG 的血清中，这些差异仍然存在。TIGR4(-)+6A 和 +23F 菌株的中性粒细胞吞噬作用也增加，但仅在补体存在的情况下，表明荚膜血清型对 C3b/iC3b 沉积的影响在功能上是显著的。此外，TIGR4(-)+6A 和 +23F 菌株在败血症的小鼠模型中的毒力降低。这些数据表明，对补体介导的免疫的抗性可以随荚膜血清型而变化，与抗体和菌株之间的其他遗传差异无关。这可能是荚膜血清型影响不同肺炎链球菌菌株相对侵袭性的一种机制。
