Severe gingivitis has been linked to the development of chronic obstructive pulmonary disease, or COPD. However, it is not fully understood how the connection plays out in the immune system. Now, a new study reveals immune system cells that play a key role in the microbial link between COPD and gum disease. Researchers from Sichuan University, China, report that bacteria associated with gum disease promote COPD by activating two types of cells, γδ T cells and M2 macrophages.
The findings are published in mSystems in an article entitled “Periodontitis exacerbates COPD through activation of γδ T cells and M2 macrophages.”
“COPD is a chronic systemic inflammatory disease with high morbidity and mortality,” the researchers wrote. “Periodontitis worsens the progression of COPD. However, the immunological mechanisms by which periodontitis affects COPD remain unclear. Here, by constructing mouse models of periodontitis and COPD, we showed that periodontitis and COPD could mutually exacerbate disease progression. For the first time, we found that progression was linked to activation of γδ T cells and M2 macrophages, and M2 polarization of macrophages was affected by γδ T cell activation.”
“By enhancing periodontal therapy and targeting inhibition of γδ T cells and M2 macrophages [we] may help control the progression of COPD,” said microbiologist Boyu Tang, PhD, who led the study with microbiologist Yan Li, PhD.
Periodontitis is a chronic infectious disease, and previous studies have found it to be a risk factor for a number of diseases, including diabetes, hypertension, certain cancers, cardiovascular disease, and COPD.
Previous studies, including some led by Li and Tang, have shown that oral bacteria Porphyromonas gingivalis plays an important role in gum disease. For the current study, Li, Tang and colleagues used mouse models to show how these bacteria could worsen the progression of COPD. In one experiment, they showed that mice infected with both periodontitis and COPD had worse progression of COPD than mice infected only with COPD.
In another experiment, they observed that in mice that were infected orally P. gingivalis, the bacteria migrated and infected the lung tissue, leading to a significant, observable change in the lung microbiota. Further observations using flow cytometry and immunofluorescence revealed that periodontitis promoted the expansion of immune cells in lung tissue. Finally, in experiments using mouse lung tissue, the team connected the dots by showing that P. gingivalis could activate immune system cells, promoting their ability to produce cytokines associated with worsening COPD.
The researchers observed that the decrease in lung function and increase in immune cells was more modest than they had predicted, but this could be an artifact of the experimental setup. The team created animal models of COPD using exposure to cigarette smoke. “If exposure to cigarette smoke could be extended for a longer period of time, these changes may be more pronounced,” Lee said. In future studies, Li said the team plans to investigate how increasing exposure to smoke might affect the immune response.
“We will further conduct additional human studies to confirm the mechanism,” Li said. They plan to recruit patients with both conditions and offer periodontitis treatment, then compare lung function and immune cell counts before and after. “Our finding could lead to a potential new strategy for the treatment of COPD.”
