Implant-associated infection induces systemic immune reprogramming

Implant-associated infection (IAI) is a formidable clinical challenge characterized by high recurrence despite aggressive surgery and antimicrobial therapy. IAI is not merely a localized microbiological crisis but also a systemic immune-metabolic disorder driven by a pathological local-systemic pathogen-host axis. Here, we propose an IAI osteoimmune cascade model of disease progression. In phase I (local), pathogen invasion and biofilm formation disrupt osteoimmune homeostasis, establishing protected niches and initiating continuous pathological crosstalk among invading pathogens, resident bone cells and immune cells. In phase II (hematopoietic), local signals propagate via vesicular trafficking, humoral networks, and neural regulatory routes to the bone marrow, inducing metabolic-epigenetic rewiring in hematopoietic stem and progenitor cells to imprint myeloid skewing and lymphoid suppression. In phase III (systemic), reprogrammed myeloid cells are continuously exported to the periphery to promote myeloid-derived suppressor cell expansion and terminal exhaustion of T cells, while local metabolic restriction suppresses residual pathogen clearance. This tripartite cascade model demonstrates that conventional microbial eradication alone cannot reverse established immune dysfunction. Based on these insights, we propose a precision immune-guided surgical framework based on immune reconstitution to overcome therapeutic recalcitrance by redefining IAI as a systemic immune-metabolic disorder.