Proteomic profiling links neutrophil extracellular traps to periprosthetic joint infection
Investigators compared the proteomes of sonicate fluids from revision arthroplasty specimens using LC-MS/MS and proximity extension assays to characterize immune responses in periprosthetic joint infection versus non-infectious arthroplasty failure. Analysis of 85 infected and 26 non-infectious samples by mass spectrometry, alongside 95 and 39 samples by proximity extension assay, revealed that neutrophil extracellular trap formation and neutrophil degranulation are significantly associated with infection, with complement cascade and platelet activation pathways implicated. In vitro experiments further demonstrated that synovial fluid components delay neutrophil extracellular trap formation compared to standard culture media. These findings establish a mechanistic framework for infection pathogenesis and highlight proteomic signatures that could inform future diagnostic and therapeutic strategies for joint infections.
The original study
Metaproteomic analysis of human sonicate fluid highlights neutrophil extracellular trap formation associated with periprosthetic joint infection.
- Authors
- Garcia E, O'Connor K, Koscianski C, Alvarez Otero J, O'Donnell K, Mangalaparthi KK, et al.
- Journal
- Microbiology spectrum
- Type
- Journal Article
- PMID
- 42867249
Original abstract
UNLABELLED: Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty that can be challenging to diagnose and treat. Neutrophils are a prominent feature in PJI, with neutrophil extracellular traps (NETs) known to be present; little is known, however, about the physiology of PJI-associated NETs. Here, the proteomes of PJI and non-infectious arthroplasty failure (NIAF), analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS) and proximity extension assay (PEA)-based profiling of fluids derived from sonication of arthroplasty components removed from patients who had undergone revision arthroplasty, were compared, with a focus on NET formation. In addition, in vitro effects of synovial fluid components on Staphylococcus aureus-induced NET formation were characterized. LC-MS/MS (PJI n = 85, NIAF n = 26) and PEA (PJI n = 95, NIAF n = 39) showed NET formation and neutrophil degranulation to be associated with PJI, with the complement cascade and platelet activation pathways identified as potential contributors. In vitro studies showed delayed NET formation in artificial synovial fluid compared to standard cell culture media conventionally used to evaluate NETs. Together, these results demonstrate the presence of NETs in PJI, identify potential pathways involved in PJI-associated NETosis, and point to an influence of synovial components on NET formation during PJI. IMPORTANCE: Periprosthetic joint infection (PJI) is a major complication of joint replacement, placing a significant burden on patients and the healthcare system. Our research reveals that neutrophils and their antimicrobial "traps" are dominant features of the immune response at the infection joint site. Importantly, we found that the unique environment of the joint delays the formation of these traps, potentially contributing to the pathogenesis of PJI. By establishing a new experimental platform tailored for the infected joint, this work provides a foundational platform for probing these mechanisms and supports the development of improved diagnostic and therapeutic strategies.