Neisseria bacilliformis is a periodontal pathogen exacerbating periodontitis by inducing nitric oxide production

Periodontitis, a chronic inflammatory disease, often causes alveolar bone loss. <i>Neisseria bacilliformis</i> is a Gram-negative bacterium that has been identified in periodontal patients, but its role in periodontitis remains unclear. In the present study, we examined whether <i>N. bacilliformis</i> exacerbates periodontitis in a mouse ligature-induced periodontitis (LIP) model and investigated its underlying molecular mechanism. Topical treatment with <i>N. bacilliformis</i> on maxillary second molar exacerbated alveolar bone loss and worsened epithelial and periodontal ligament damage. Histological analyses showed that <i>N. bacilliformis</i> increases tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and inducible nitric oxide synthase (iNOS) levels in the gingival tissue. Treatment with <i>N. bacilliformis</i> induced nitric oxide (NO) production in RAW 264.7 cells, which was inhibited by polymyxin B, implying that <i>N. bacilliformis</i> lipooligosaccharide (LOS) is a major etiologic agent in the inflammatory response. Indeed, LOS purified from <i>N. bacilliformis</i> enhanced NO production and iNOS expression, primarily with activating Toll-like receptor (TLR) 4 and partially activating TLR2. LOS administration into the disto-palatal papilla near the molar further aggravated periodontitis in the LIP mouse model. These results suggest that <i>N. bacilliformis</i> is a periodontal pathogen that exacerbates inflammation and alveolar bone loss, with its LOS acting as an important virulence factor via TLR2/4 activation, leading to the production of the inflammatory mediator NO.