Periodontitis aggravates COPD through the activation of γδ T cell and M2 macrophage

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease with high morbidity and mortality. Periodontitis exacerbates COPD progression; however, the immune mechanisms by which periodontitis affects COPD remain unclear. Here, by constructing periodontitis and COPD mouse models, we demonstrated that periodontitis and COPD could mutually aggravate disease progression. For the first time, we found that the progression was associated with the activation of gamma delta T cells and M2 macrophages, and M2 polarization of macrophages was affected by gamma delta T cells activation. In the lung tissues of COPD with periodontitis, the activation of gamma delta T cells finally led to the increase of IL 17 and IFN gamma expression and M2 macrophage polarization. Furthermore, we found that the periodontitis-associated bacteria Porphyromonas gingivalis (P. gingivalis) promoted the activation of gamma delta T cells and M2 macrophages ex vivo. The data from clinical bronchoalveolar lavage fluid (BALF) samples were consistent with the in vivo and ex vivo experiments. For the first time, our results identified the crucial role of gamma delta T-M2 immune mechanism in mediating periodontitis-promoted COPD progression. Therefore, targeting at periodontitis treatment and the gamma delta T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control. IMPORTANCE Periodontitis exacerbates chronic obstructive pulmonary disease (COPD) progression. For the first time, the current study identified that the impact of periodontitis on COPD progression was associated with the activation of gamma delta T cells and M2 macrophages and that M2 polarization of macrophages was affected by gamma delta T cells activation. The results indicated that targeting at periodontitis treatment and the gamma delta T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control.