Staphylococcus epidermidis prosthetic joint infections are associated with an expansion of distinct immune cell populations

Staphylococcus epidermidis is a leading pathogen in prosthetic joint infections (PJI). Biofilm formation plays a key role in S. epidermidis immune evasion and is essential for the development of chronic, therapy-resistant infections. In PJI, the host mounts a significant immune response, mainly characterized by infiltration of the joint and synovial fluid (SF) by neutrophils. In addition, myeloid-derived suppressor cells (MDSCs) are increased in the SF of infected prosthetic joints and are important in dampening the proliferation and activation of other leukocytes such as NK or T cells. Own evidence from in vitro studies supports the idea that in S. epidermidis implant infections, biofilm formation induces the development of anti-inflammatory macrophages. While this mechanism might be relevant for chronic infections, at present the importance in vivo is unknown. Therefore, the major aim of this study was provide a high resolution population analysis of immune cells in the SF from S. epidermidis PJI.

To study immune cell distribution SF and whole blood were obtained from seven patients (two female, five male) undergoing revision arthroplasty of the knee (n=4) or hip (n=3) for late chronic PJI by S. epidermidis. Flow cytometric analysis of SF revealed a consistent increase in monocytes (especially CD14^dim), conventional dendritic cells (type 1 and 2) and chronically activated CD4⁺ T cells as compared to the corresponding blood sample. Plasmacytoid dendritic cells did not change significantly between SF and blood samples.

The higher levels of non-classical monocytes and CD127^neg CD4⁺ T cells may represent a state of chronic infection that cannot be cleared by immune cells due to biofilm formation of the pathogen. In order to investigate the interaction between S. epidermidis and immune cells in the infected joint, we are currently analyzing the differentiation profile and cytokine production of the infiltrating monocytes in relation to virulence factors of the patient-isolated S. epidermidis strains.