LL-37 and bacterial DNA complexes in dental plaque: Implications for biofilm structure, innate immunity, and periodontal pathogenesis

BACKGROUND: Dental plaque is a highly organized polymicrobial biofilm, in which extracellular DNA serves as a vital structural and functional component of the extracellular matrix. The human antimicrobial peptide LL-37 plays an important role in oral innate defense, exhibiting both antimicrobial and immunomodulatory activities. Our recent study indicated that LL-37 forms stable complexes with bacterial DNA in dental plaque. This review summarizes current knowledge of the molecular mechanisms and immunological consequences of LL-37-bacterial DNA interactions in dental plaque, highlighting their potential implications in biofilm structure, innate immunity, and periodontal pathogenesis. HIGHLIGHT: LL-37 binds to oral bacterial DNA forming stable, nuclease-resistant, high-molecular-weight complexes with an aggregated morphology. These complexes abrogate the intrinsic antimicrobial activity of LL-37 while enhancing the stability and cohesiveness of the biofilm matrix. Moreover, LL-37-bacterial DNA complexes act as immunostimulatory molecules by activating TLR9 and the NLRP3 inflammasome, thereby triggering proinflammatory cytokine production in host immune cells. Notably, this immunostimulatory capacity varies with the bacterial source of the DNA, suggesting species-specific modulation of host responses. CONCLUSION: LL-37-bacterial DNA complex formation represents a key event at the interface of innate defense and dysbiosis in dental plaque. This dual nature of LL-37, whereby it acts as an antimicrobial peptide when alone, yet promotes biofilm formation and inflammation when complexed with bacterial DNA, sheds new light on the mechanisms underlying biofilm persistence and chronic inflammation. Understanding this interaction may open new avenues for therapeutic strategies targeting biofilm-associated periodontal diseases.