Porphyromonas gingivalis and Scardovia wiggsiae promote neutrophil-induced lung epithelial cell apoptosis and emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with bronchitis and pulmonary emphysema phenotypes, with high morbidity and mortality. COPD is predicted to be the third leading cause of death by 2030. Periodontitis results from oral microbe dysbiosis, such as enrichment of periodontitis pathogens (e.g., Porphyromonas gingivalis), which could disseminate to the lung via the blood stream or aspiration. Periodontitis pathogens are suggested to contribute to chronic inflammation and mucin secretion in the lung. Accordingly, periodontitis pathogens are associated with the pathogenesis and progression of COPD. However, clinical observation of a correlation between COPD and periodontitis is limited and the involved mechanism is not fully understood.

METHODS: We used a mouse model with ligature-induced periodontitis and porcine pancreatic elastase (PPE)-induced pulmonary emphysema to evaluate the roles of P. gingivalis and Scardovia wiggsiae in COPD progression. We analyzed proinflammatory cytokines, immune cells, apoptosis, and the extent of COPD progression using a multiplex assay/enzyme-linked immunosorbent assay, Hemacolor kit, terminal deoxynucleotidyl transferase nick-end labeling assay, and the mean linear intercept and lung function, respectively.

RESULTS: The results suggest that both oral bacterial species contributed to the periodontitis phenotype, promoted PPE-induced proinflammatory cytokines in serum and bronchoalveolar lavage, and facilitated neutrophil infiltration in the lung. The abundance of neutrophils increased neutrophil elastase (NE) and downstream placenta growth factor (PGF) in the lung and led to alveolar epithelial cell apoptosis, pulmonary emphysema and lung function decline in the PPE-treated mice. All pathological phenotype were attenuated by Ly6G antibody-mediated neutrophil depletion in mice.

CONCLUSIONS: We demonstrated a potential mechanism for periodontal-associated progression to COPD via the neutrophil-NE-PGF pathway.

PLAIN LANGUAGE SUMMARY: We demonstrated that the oral bacteria Porphyromonas gingivalis and Scardovia wiggsiae exacerbate ligature-induced inflammation and increase proinflammatory cytokines in local gingival crevicular fluid, systemic serum, and distal bronchoalveolar lavage, and are associated with more neutrophil infiltration in the lung. The in vivo experiment indicated that gingival infection with P. gingivalis and S. wiggsiae worsens porcine pancreatic elastase-induced pulmonary apoptosis and emphysema. Here, we show that P. gingivalis and S. wiggsiae are potential pathogenic factors for COPD.