{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:01:31Z","timestamp":1791198091116,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Orthopedic implant biofilms are not only antibiotic-tolerant bacterial communities but metabolically active niches that reshape host immunity. Compared with planktonic infection, mature biofilms impose spatial and metabolic constraints that can uncouple leukocyte recruitment from sterilizing activity. Neutrophils can penetrate and phagocytose portions of Staphylococcus aureus biofilms, but clearance becomes incomplete as biofilms mature and may coexist with degranulation and neutrophil extracellular trap-associated tissue injury. Macrophages show impaired access and bactericidal programming, and biofilm-derived lactate can promote interleukin-10 (IL-10) through histone deacetylase 11 (HDAC11)\/HDAC6-dependent epigenetic reprogramming in experimental systems. Human periprosthetic joint infection (PJI) tissues are enriched in granulocytic myeloid-derived suppressor cells (G-MDSCs), whereas the glycolysis\/hypoxia-inducible factor 1-alpha (HIF-1alpha) phenotype and its contribution to persistence are supported primarily by murine PJI, with limited human transcriptomic corroboration. In chronic S. aureus infection models, MDSC-derived lactate can suppress CD4-positive (CD4+) T-cell glycolysis; conversely, immune pressure drives heterogeneous bacterial metabolic, stress-response, and virulence programs. We synthesize these interactions as bidirectional biofilm-host immunometabolic crosstalk linking persistent infection to bone-interface damage. Source control and antibiotics remain essential. Local, time-limited, dysfunction-directed host interventions are presented here as a hypothesis-generating translational framework rather than evidence-based clinical recommendations, because host-directed immunometabolic therapies for PJI remain preclinical.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1957346","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:29:32Z","timestamp":1791196172000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biofilm-host immunometabolic crosstalk in Staphylococcus aureus orthopedic implant infection: mechanisms and translational constraints"],"prefix":"10.3389","volume":"17","author":[{"given":"Jixin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Shaoxing Shangyu District Hospital of Traditional Chinese Medicine","place":["Shaoxing, 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