Streptococcus pneumoniae Resistance to Complement-Mediated Immunity Is Dependent on the Capsular Serotype
Streptococcus pneumoniae Resistance to Complement-Mediated Immunity Is Dependent on the Capsular Serotype
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DOI：
10.1128/iai.01056-09
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发表时间：
2010-02-01
影响因子：
3.1
通讯作者：
Brown, Jeremy S.
中科院分区：
文献类型：
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作者：
Hyams, Catherine;Yuste, Jose;Brown, Jeremy S.
肺炎链球菌菌株在引起人类侵袭性疾病的能力上有很大的差异，这在一定程度上与被膜血清型有关。肺炎链球菌胶囊抑制补体和吞噬细胞介导的免疫，这些影响宿主免疫的血清型之间的差异可能导致菌株之间毒力的一些差异。然而，肺炎链球菌不同于被膜血清型的显著遗传差异阻碍了使用临床分离株对被膜血清型对免疫的影响的明确评估。因此，我们使用被膜血清型转换的TIGR4突变株来研究被膜血清型对肺炎链球菌与补体相互作用的影响。流式细胞仪分析显示，TIGR4(-)+4、+6A、+7F和+23F株的不透明相变异株的C3b/iC3b沉积有很大差异，尽管被膜层的厚度相似。与+7F和+4株相比，TIGR4(-)+6A和+23F株的C3b/iC3b沉积增加，即使在免疫球蛋白G耗尽的血清中这种差异仍然存在，TIGR4(-)+6A和+23F株的中性粒细胞吞噬能力也增加，但仅在补体存在时，这表明衣壳血清型对C3b/iC3b沉积的影响是显著的。此外，在脓毒症小鼠模型中，TIGR4(-)+6A和+23F菌株的毒力降低。这些数据表明，对补体介导的免疫的抵抗力可以随着衣壳血清型的不同而不同，独立于抗体和菌株之间的其他遗传差异。这可能是衣壳血清型影响不同肺炎链球菌相对侵袭力的机制之一。
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.