Immune-based strategies for the treatment of biofilm infections

Biofilms are bacterial communities surrounded by a polymeric matrix that can form on implanted materials and biotic surfaces, resulting in chronic infection that is recalcitrant to immune- and antibiotic-mediated clearance. Therefore, biofilm infections present a substantial clinical challenge, as treatment often involves additional surgical interventions to remove the biofilm nidus, prolonged antimicrobial therapy to clear residual bacteria, and considerable risk of treatment failure or infection recurrence. These factors, combined with progressive increases in antimicrobial resistance, highlight the need for alternative therapeutic strategies to circumvent undue morbidity, mortality, and resource strain on the healthcare system resulting from biofilm infections. One promising option is reprogramming dysfunctional immune responses elicited by biofilm. Here, we review the literature describing immune responses to biofilm infection with a focus on targets or strategies ripe for clinical translation. This represents a complex and dynamic challenge, with context-dependent host-pathogen interactions that differ across infection models, microenvironments, and individuals. Nevertheless, consistencies among these variables exist, which could facilitate the development of immune-based strategies for the future treatment of biofilm infections.