Cytokine and chemokine dysregulation by biofilm components.

Biofilms pose a major challenge in oral and systemic infections due to their capacity to evade host defences and modulate immune responses. Dysregulated cytokine and chemokine signaling induced by biofilm components plays a central role in disease progression, particularly in chronic conditions such as periodontitis, cystic fibrosis, and non-healing wounds. In periodontal disease, the shift from microbial homeostasis to dysbiosis is marked by enhanced pathobiont virulence, elevated inflammatory mediators including IL-6, IL-1β, TNF-α, and CXCL8, and a bias toward pro-inflammatory macrophage polarization. Localized aggressive periodontitis exhibits an exaggerated inflammatory response to bacterial surface molecules and biofilm-derived products, highlighting distinct mechanisms of immune activation. In systemic infections, biofilms facilitate immune evasion through metabolic reprogramming of macrophages and neutrophils, sustaining chronic inflammation and tissue damage. Persistent biofilms in cystic fibrosis lungs, chronic wounds, and medical device-associated infections further illustrate the complex host-microbe interactions, where excessive neutrophil infiltration and prolonged cytokine release aggravate pathology. Moreover, biofilm constituents can suppress protective immune responses, creating an immunosuppressive microenvironment that favours bacterial persistence. This review summarizes current insights into biofilm-mediated immune modulation, emphasizing key cytokine and chemokine alterations across disease contexts and discussing emerging therapeutic strategies aimed at restoring immune homeostasis and improving clinical outcomes.