Overcoming the immune inhibitory environment associated with Staphylococcus aureus biofilms by activated macrophage transfer (166.6)

Abstract

Abstract Staphylococcus aureus (S. aureus) can establish biofilm infections on natural and artificial surfaces, which are typically recalcitrant to antibiotic therapy. Our laboratory has shown that S. aureus biofilms evade macrophage (MΦ) anti-microbial activity, further complicating biofilm eradication. To overcome the local immune inhibitory environment created by S. aureus biofilms, we have examined whether local administration of IFN-γ and peptidoglycan activated MΦs facilitates biofilm clearance in vivo using two treatment paradigms. In a prophylactic approach, mice received activated MΦs at 12, 24, and 48 h post-infection, whereupon bacterial burdens on infected catheters and surrounding tissues were quantitated at days 3 or 14 post-infection to evaluate the longevity of MΦ-mediated biofilm clearance. For established biofilms, activated MΦs were introduced at days 7 and 9 post-infection. In both treatment paradigms, activated MΦs led to significant reductions in bacterial burdens on infected catheters and catheter-associated tissues compared to vehicle controls. In addition, many proinflammatory mediators were significantly elevated in MΦ-treated animals in both models, indicating that MΦ administration is capable of overcoming the local immune inhibitory environment created during S. aureus biofilm formation. Collectively, these findings demonstrate that the local administration of activated MΦs enhances the host immune response to facilitate S. aureus biofilm clearance.