aureus Newman Δlgt mutant strain (WT/ Δlgt and TLR2 −/−/ Δlgt, respectively). aureus Newman parental strain expressing Lpp (WT/Newman and TLR2 −/−/Newman, respectively) or S. aureus Lpp and the influence of TLR2 deficiency on the severity and frequency of clinical arthritis, wild-type (WT) and TLR2 deficient (TLR2 −/−) mice were intravenously inoculated with an arthritic dose of either S. Staphylococcal lipoproteins induce more severe and frequent clinical septic polyarthritis in TLR2 deficient mice aureus systemic infection, independently of TLR2, but their effect on radiological bone erosion is limited. Our findings demonstrate that expression of staphylococcal Lpp increases the virulence of S. In the present study, we investigated the role of staphylococcal Lpp as well as TLR2 in our well-established hematogenous mouse model of S. It still remains unclear whether staphylococcal Lpp enhance disease severity in hematogenous septic arthritis. However, it is well-known that the majority of septic arthritis in patients is caused by hematogenous spreading of bacteria 11. aureus Lpp, when injected intra-articularly into the mouse knee joints, induced destructive arthritis in TLR2-dependent manner 6. In a recent study, we demonstrated that purified S. aureus infections has been studied in different infection models, including sepsis and skin infection 6, 19, 20, 21, 22. The lipid structure of Lpp is known to stimulate the innate immune system through activation of pattern recognition receptors 15, and bacterial Lpp are predominant ligands for Toll-like receptor 2 (TLR2) 16, 17, 18. Lpp are important for bacterial survival during infection due to their role in maintaining the metabolic activity of the bacteria 13, 14. aureus, consist of a lipid-moiety and a protein-part, and are anchored in the bacterial cytoplasmic membrane 12. Staphylococcal lipoproteins (Lpp), important bacterial molecules in S. However, much still remains elusive regarding the bacteria-host interaction in S. aureus-induced septic arthritis has been extensively studied for the past few decades several virulence factors as well as various host-factors targeted by the bacterium have been identified 6, 7, 8, 9, 10, 11. aureus), a pathogenic Gram-positive bacterium 5. Septic arthritis is most often caused by Staphylococcus aureus ( S. However, in patients with an underlying joint disease, such as rheumatoid arthritis (RA), the incidence of septic arthritis is nearly 10 times higher than in the general population 4. The estimated incidence of septic arthritis in the general population is approximately 6–10 cases per 100,000 individuals per year 4. Almost half of the patients will suffer from permanent joint destruction 2, if treatment is not initiated immediately 3. Despite advances in understanding and treatment of infectious diseases, the prospect of patients with septic arthritis has remained poor. Due to its rapidly progressing nature, septic arthritis is considered a medical emergency 1 with a poor prognosis. Septic arthritis remains a devastating and invasive joint disease. However, they have a limited impact on bone erosion in hematogenous staphylococcal septic arthritis. aureus systemic infection independent of host TLR2 signalling. Staphylococcal Lpp are potent virulence factors in S. Furthermore, Lpp expression induced increased systemic pro-inflammatory cytokine and neutrophil chemokine release. Lpp expression was associated with higher mortality, weight loss as well as impaired bacterial clearance in mouse kidneys independent of TLR2. Bone destruction, however, did not differ between groups. Newman strain induced more severe and frequent clinical septic polyarthritis compared to its Δlgt mutant in TLR2 deficient mice, but not in wild-type controls. The clinical course of septic arthritis, radiological changes, and serum levels of cytokines and chemokines, were assessed. aureus Newman parental strain or its lipoprotein-deficient Δlgt mutant strain. C57BL/6 wild-type and TLR2 deficient mice were intravenously inoculated with S. aureus Lpp and TLR2 in a hematogenous septic arthritis model, which is the most common route of infection in humans. Here, we aim to investigate the importance of S. aureus) lipoproteins (Lpp), the predominant ligands for TLR2, are known to be arthritogenic and induce bone destruction when introduced directly into the joint. Permanent joint dysfunction is a devastating complication in patients with septic arthritis.
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