Porphyromonas gingivalis Components/Secretions Synergistically Enhance Pneumonia Caused by Streptococcus pneumoniae in Mice

Teppei Okabe,Noritaka Sawada,Yoshihiko Sugita,Takeshi Kikuchi,Akio Mitani,Yoshikazu Naiki,Jun-Ichiro Hayashi,Yoshiaki Hasegawa,Naoya Higuchi,Shotaro Kawamura,Masayuki Umemura,Takeki Fujimura,Hisashi Goto,Yuhei Takayanagi,Yuki Suzuki,Yosuke Kamiya

doi:10.3390/ijms222312704

Abstract

Streptococcus pneumoniae is an important causative organism of respiratory tract infections. Although periodontal bacteria have been shown to influence respiratory infections such as aspiration pneumonia, the synergistic effect of S. pneumoniae and Porphyromonas gingivalis, a periodontopathic bacterium, on pneumococcal infections is unclear. To investigate whether P. gingivalis accelerates pneumococcal infections, we tested the effects of inoculating P. gingivalis culture supernatant (PgSup) into S. pneumoniae-infected mice. Mice were intratracheally injected with S. pneumoniae and PgSup to induce pneumonia, and lung histopathological sections and the absolute number and frequency of neutrophils and macrophages in the lung were analyzed. Proinflammatory cytokine/chemokine expression was examined by qPCR and ELISA. Inflammatory cell infiltration was observed in S. pneumoniae-infected mice and S. pnemoniae and PgSup mixed-infected mice, and mixed-infected mice showed more pronounced inflammation in lung. The ratios of monocytes/macrophages and neutrophils were not significantly different between the lungs of S. pneumoniae-infected mice and those of mixed-infected mice. PgSup synergistically increased TNF-α expression/production and IL-17 production compared with S. pneumoniae infection alone. We demonstrated that PgSup enhanced inflammation in pneumonia caused by S. pneumoniae, suggesting that virulence factors produced by P. gingivalis are involved in the exacerbation of respiratory tract infections such as aspiration pneumonia.

Highlights

Pneumonia is a globally common infection and a major cause of death, as highlighted by the impact of coronavirus disease 2019 (COVID-19) [1,2]
Inflammation was induced by S. pneumoniae (Sp) infection alone, it was observed that the inflammation was exacerbated by the presence of P. gingivalis culture supernatant (PgSup)
Our results suggested the possibility that the lung infection in mice inoculated with S. pneumoniae and PgSup might be caused by gingipains produced by P. gingivalis, which damage the extracellular matrix of alveolar epithelial cells and facilitate the entry of S. pneumoniae into the tissues, thereby increasing the inflammatory reaction

Summary

Introduction

Pneumonia is a globally common infection and a major cause of death, as highlighted by the impact of coronavirus disease 2019 (COVID-19) [1,2]. The oral bacterial species implicated in causing pneumonia and lung abscesses are Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Actinomyces israelii, Capnocytophaga species, Eikenella corrodens, Prevotella intermedia, and Streptococcus constellatus [7]. These bacteria are closely associated with oral disease and oral hygiene. Recent reports have questioned the quality of the evidence indicating that professional oral care reduces pneumonia mortality compared with regular care in nursing home residents, and so caution is required in interpreting the results, as no conclusions have been reached regarding other outcomes effective in reducing pneumonia [10]. Regarding the relationship between S. pneumoniae and oral hygiene, Okuda and coworkers reported that oral lavage significantly decreased the percentage of S. pneumoniae bacteria detected in patients who underwent oral and maxillofacial surgery [11]

Objectives

Methods

Results

Discussion

Conclusion