Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies – including biofilm formation, small colony variants, and inhibition of phagolysosomal killing – further enhance persistence and immune evasion. While these mechanisms are well studied in extracellular infections, their role in intracellular survival is increasingly evident. This review synthesizes emerging insights into how S. aureus manipulates macrophage function to establish chronic bone infection and highlights therapeutic opportunities targeting macrophage polarization to improve immune-mediated clearance and bone repair in osteomyelitis.
Lathram et al. (2025) studied this question.