Progress in Research on Macrophage Polarization Mechanisms and Targeted Therapies in Staphylococcus aureus Infections.

Staphylococcus aureus is a clinically prevalent, Gram-positive pathogen that can cause multiple severe infections. Macrophage polarization plays a central role in host defense and inflammatory regulation, with its M1/M2 dynamic equilibrium directly determining infection outcomes. The M1 phenotype eliminates pathogens through pro-inflammatory responses in the early phase, but excessive activation readily leads to tissue damage. In contrast, the M2 phenotype suppresses inflammation and promotes healing during the repair phase, although it may become a pathogen refuge in chronic infections. Recent studies have elucidated the roles of PAMPs, virulence factors, immunometabolism, and epigenetics in regulating polarization and have explored intervention strategies involving stem cells, exosomes, nanodelivery, novel formulations, and natural medicines, offering new avenues to overcome antibiotic limitations. However, existing evidence remains confined to animal studies, and challenges related to polarization heterogeneity and clinical translation require urgent resolution. This review summarizes the mechanisms of macrophage polarization and targeted therapeutic advances in the context of S. aureus infection, aiming to provide insights for immune interventions against drug-resistant infections.