Biofilm-Induced Inflammation in Chronic Infections: Molecular Mechanisms, Host-Pathogen Interactions, and Emerging Therapeutic Strategies

Abstract

Context: Biofilms are structured microbial communities encased in a self-produced extracellular polymeric matrix that adheres to biological or abiotic surfaces. Biofilm formation is a major survival strategy for pathogenic microorganisms and plays a crucial role in the persistence of chronic infections. Unlike planktonic bacteria, biofilm-associated microorganisms exhibit increased resistance to host immune responses and antimicrobial agents, leading to prolonged inflammation and tissue damage. Evidence Acquisition: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, encompassing studies published between 2000 and 2025. Relevant original articles, systematic reviews, and clinical studies that examined biofilm formation, host immune responses, inflammatory pathways, and emerging therapeutic strategies were analyzed. Results: Biofilm formation induces persistent activation of host immune responses through multiple molecular pathways, including Toll-like receptor (TLR) signaling, nuclear factor-kappa B (NF-κB) signaling, mitogen-activated protein kinase (MAPK) pathways, and NLRP3 inflammasome activation. These mechanisms promote the production of proinflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), thereby sustaining chronic inflammation and tissue damage. Biofilm-associated infections are implicated in chronic wounds, implant-associated infections, cystic fibrosis lung infections, urinary tract infections, and persistent endodontic infections. Emerging therapeutic strategies target both biofilm architecture and inflammatory responses, including quorum-sensing inhibitors, enzymatic biofilm disruption, natural bioactive compounds, nanotechnology-based delivery systems, and host-directed therapies. Conclusions: Biofilm-induced inflammation is a critical contributor to the pathogenesis and persistence of chronic infectious diseases. Elucidating the molecular interactions between microbial biofilms and host immunity can provide valuable insights to inform the development of innovative therapies. Future research should prioritize integrated antibiofilm and anti-inflammatory interventions to improve treatment outcomes and reduce the global burden of chronic infections.