Cytokine and chemokine dysregulation by microbial biofilm components: mechanisms and clinical implications.

Biofilm-associated infections represent a major clinical and biological challenge due to their ability to persist within host tissues while evading immune clearance and antimicrobial therapy. These structured microbial communities profoundly alter host immune signaling, particularly cytokine and chemokine networks, leading to sustained inflammation and tissue damage. Despite advances in antimicrobial development, biofilms continue to undermine treatment efficacy by promoting antibiotic resistance, dysregulated gene expression, and chronic inflammatory states, especially in wounds, implanted medical devices, and respiratory infections. Key challenge lies in complex bidirectional interactions between biofilm components and host immune pathways, which result in maladaptive immune responses rather than effective pathogen elimination. The novelty of this study lies in its integrated analysis of biofilm-mediated cytokine and chemokine dysregulation across bacterial and fungal biofilms, emphasizing molecular mechanisms, immune cell reprogramming, and host-specific determinants of disease progression. The purpose of this work is synthesizing current evidence on how biofilms modulate inflammatory signaling; identify critical regulatory pathways involved in chronic infection, highlighting emerging therapeutic strategies targeting both microbial persistence and immune imbalance. Major outcomes include bacterial biofilms like Pseudomonas aeruginosa, Staphylococcus aureus, and polymicrobial wound biofilms, illustrating altered cytokine profiles, immune gene regulation, delayed wound healing, and tissue remodeling. The review also addresses biofilm-driven immune dysfunction in chronic wounds and respiratory diseases, linking molecular signaling events to clinical outcomes. Hence, understanding cytokine and chemokine dysregulation in biofilm-associated infections is essential for the development of immune-informed, personalized therapeutic strategies, and future interventions must integrate antimicrobial, antibiofilm, and immunomodulatory approaches to achieve durable clinical success.