Bacteria-induced immunity: from homeostasis to immune subversion in periodontitis

This review synthesizes current evidence on host immune responses to bacteria, their roles in the development and progression of periodontitis, and emerging immunomodulatory therapeutic strategies designed to restore periodontal homeostasis. Periodontitis develops through interactions between a dysbiotic bacterial community that disrupts host-microbe homeostasis and a chronic, maladaptive interaction with the host immune system. Key immune subversion microorganisms such as Porphyromonas gingivalis trigger inflammation while subverting immune surveillance by evading complement-mediated clearance and impairing neutrophil function. This dual behavior creates a biological paradox: bacteria induce inflammation to obtain nutrients while simultaneously suppressing effective antimicrobial activity, thereby perpetuating chronic, tissue-destructive immune activation. The osteoimmune response, particularly the Th17/IL-17 axis, is a central pathway linking microbial dysbiosis to persistent inflammation and alveolar bone resorption. These findings suggest that successful periodontal therapy must extend beyond mechanical biofilm removal by addressing underlying immune dysregulation. Potential adjunctive strategies for modulating this response include specialized pro-resolving mediators, complement inhibitors such as Cp40, and selected probiotics with immunoregulatory properties. Collectively, these approaches are intended to restore immune balance, enhance resolution of inflammation, and promote periodontal tissue repair. Current evidence demonstrates that periodontitis is not solely a microbial infection but also involves dysregulated host immunity. Clarifying how bacteria manipulate immune pathways may facilitate the development of therapies that complement bacterial control by targeting the inflammatory mechanisms underlying tissue destruction. Immunomodulatory interventions therefore represent promising candidates for promoting sustained periodontal stability and inflammatory resolution.