Division of Infectious Diseases, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Hum Immunol. 2011 Jan;72(1):47-53. doi: 10.1016/j.humimm.2010.10.001. Epub 2010 Oct 28.
Staphylococcus aureus induces inflammation in experimental models through Toll-like receptor 2 (TLR2). The clinical relevance of this observation is debated. We evaluated the relationship between TLR2 R753Q single nucleotide polymorphism (SNP) and S aureus infection of joint prosthesis. Human embryonic kidney 293 (HEK293) cells transfected with wild-type and mutant R753Q TLR2 gene were assessed for response to S aureus peptidoglycan. Real-time polymerase chain reaction and gene sequencing of DNA were performed to assess TLR2 R753Q SNP in 76 patients with S aureus prosthetic joint infection (PJI) and 208 noninfected controls. HEK293 cells expressing wild-type TLR2 gene responded robustly to S aureus peptidoglycan, while cells with mutant R753Q TLR2 gene did not. The prevalence of R753Q SNP was high in S aureus PJI patients (heterozygous in 8%, and homozygous in 22%), although not significantly different from controls (12% and 27%, respectively). The TLR2 variant allele was not significantly associated with the risk or survival free of recurrent PJI S aureus. In conclusion, TLR2 R753Q SNP disabled the cellular response to S aureus peptidoglycan in vitro. However, TLR2 R753Q SNP was not significantly associated with the risk or outcome of PJI due to S aureus in human patients.
金黄色葡萄球菌通过 Toll 样受体 2（TLR2）诱导实验模型中的炎症。这种观察的临床相关性存在争议。我们评估了 TLR2 R753Q 单核苷酸多态性（SNP）与金黄色葡萄球菌感染关节假体之间的关系。转染野生型和突变型 R753Q TLR2 基因的人胚肾 293（HEK293）细胞被评估对金黄色葡萄球菌肽聚糖的反应。进行实时聚合酶链反应和 DNA 基因测序，以评估 76 例金黄色葡萄球菌人工关节感染（PJI）患者和 208 例未感染对照的 TLR2 R753Q SNP。表达野生型 TLR2 基因的 HEK293 细胞对金黄色葡萄球菌肽聚糖有强烈反应，而具有突变型 R753Q TLR2 基因的细胞则没有。R753Q SNP 在金黄色葡萄球菌 PJI 患者中（杂合子为 8%，纯合子为 22%）的发生率较高，尽管与对照组无显著差异（分别为 12%和 27%）。TLR2 变体等位基因与金黄色葡萄球菌 PJI 的风险或无复发性生存无关。总之，TLR2 R753Q SNP 使细胞对金黄色葡萄球菌肽聚糖的反应在体外失活。然而，TLR2 R753Q SNP 与金黄色葡萄球菌引起的 PJI 风险或结果在人类患者中无显著相关性。
