Interactions between Macrophages and Biofilm during <i>Staphylococcus aureus</i>-Associated Implant Infection: Difficulties and Solutions

<i>Staphylococcus aureus</i> (<i>S. aureus</i>) biofilm is the major cause of failure of implant infection treatment that results in heavy social and economic burden on individuals, families, and communities. Planktonic <i>S. aureus</i> attaches to medical implant surfaces where it proliferates and is wrapped by extracellular polymeric substances, forming a solid and complex biofilm. This provides a stable environment for bacterial growth, infection maintenance, and diffusion and protects the bacteria from antimicrobial agents and the immune system of the host. Macrophages are an important component of the innate immune system and resist pathogen invasion and infection through phagocytosis, antigen presentation, and cytokine secretion. The persistence, spread, or clearance of infection is determined by interplay between macrophages and <i>S. aureus</i> in the implant infection microenvironment. In this review, we discuss the interactions between <i>S. aureus</i> biofilm and macrophages, including the effects of biofilm-related bacteria on the macrophage immune response, roles of myeloid-derived suppressor cells during biofilm infection, regulation of immune cell metabolic patterns by the biofilm environment, and immune evasion strategies adopted by the biofilm against macrophages. Finally, we summarize the current methods that support macrophage-mediated removal of biofilms and emphasize the importance of considering multi-dimensions and factors related to implant-associated infection such as immunity, metabolism, the host, and the pathogen when developing new treatments.