IMMUNE DYSREGULATION IN HUMAN PERIPROSTHETIC JOINT INFECTION: INSIGHTS FROM SYNOVIAL FLUID ANALYSIS

Background A hallmark of periprosthetic joint infection (PJI) is the host's inability to eradicate invading bacteria, which leads to chronic and persistent disease courses. Evidence from in vitro and animal models, particularly in the context of staphylococcal PJI, suggests that biofilm formation contributes to this persistence by driving an anti-inflammatory immune milieu. This shift is characterized by an expansion of myeloid-derived suppressor cells (MDSCs) and a predominance of M2-like macrophages, both of which impair effective bacterial clearance. However, it remains largely unclear whether these immunological mechanisms observed experimentally also play a significant role in human PJI. Objective/Methods The major aim of this study was to characterize innate and adaptive immune responses in synovial fluid (SF) from chronic PJI. Synovial fluid and peripheral blood were obtained from 20 patients (seven female, 13 male) undergoing revision arthroplasty for proven PJI and were analysed by flow cytometry. Results Infections were caused by coagulase-negative staphylococci (ConS; n=16) or anaerobic pathogens like C. acnes and F. magna (n=4). Flow cytometry-based immune profiling revealed higher frequencies of neutrophil granulocytes, conventional dendritic cells (type 1 and 2) and chronically activated CD4pos T cells in SF compared to the corresponding blood sample. The higher levels of classical monocytes, PD1pos CD4pos and CD127neg CD4pos T cells in SF may represent a state of chronic infection that cannot be cleared by immune cells due to biofilm formation by the pathogen. A comparative analysis of monocytes in SF and blood revealed in SF a higher proportion of M2-like macrophages, typically associated with anti-inflammatory and tissue-repair functions. Consistent with this finding, the concentration of the anti-inflammatory cytokines interleukin-10 and arginase were significantly elevated in SF compared to plasma. Conclusion Our findings demonstrate that chronic PJI is characterized by a distinct locally immunosuppressive environment with chronically activated CD4 + T cells, M2-like macrophages and elevated anti-inflammatory mediators such as IL-10 and arginase. A better understanding of these immune signatures may form future diagnostic and therapeutic strategies to improve the management of PJI.