Functional assessment of Toll-like receptor 2 and its relevance in patients with Staphylococcus aureus infection of joint prosthesis

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.