Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial Cells

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a...

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Main Authors: Yuwa Takahashi, Norihisa Watanabe, Noriaki Kamio, Sho Yokoe, Ryuta Suzuki, Shuichi Sato, Toshimitsu Iinuma, Kenichi Imai
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/3/1352
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author Yuwa Takahashi
Norihisa Watanabe
Noriaki Kamio
Sho Yokoe
Ryuta Suzuki
Shuichi Sato
Toshimitsu Iinuma
Kenichi Imai
author_facet Yuwa Takahashi
Norihisa Watanabe
Noriaki Kamio
Sho Yokoe
Ryuta Suzuki
Shuichi Sato
Toshimitsu Iinuma
Kenichi Imai
author_sort Yuwa Takahashi
collection DOAJ
description Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium <i>Fusobacterium nucleatum</i> (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.
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spelling doaj.art-fe3895b9bcc14c3b8c9257b4ede16fc72023-12-03T15:14:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223135210.3390/ijms22031352Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial CellsYuwa Takahashi0Norihisa Watanabe1Noriaki Kamio2Sho Yokoe3Ryuta Suzuki4Shuichi Sato5Toshimitsu Iinuma6Kenichi Imai7Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanDepartment of Microbiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanDepartment of Microbiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanDepartment of Microbiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanDepartment of Microbiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanDepartment of Periodontology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanDepartment of Complete Denture Prosthodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanDepartment of Microbiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, JapanCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium <i>Fusobacterium nucleatum</i> (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.https://www.mdpi.com/1422-0067/22/3/1352ACE2periodontitis<i>Fusobacterium nucleatum</i>proinflammatory cytokinesSARS-CoV-2COVID-19
spellingShingle Yuwa Takahashi
Norihisa Watanabe
Noriaki Kamio
Sho Yokoe
Ryuta Suzuki
Shuichi Sato
Toshimitsu Iinuma
Kenichi Imai
Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial Cells
International Journal of Molecular Sciences
ACE2
periodontitis
<i>Fusobacterium nucleatum</i>
proinflammatory cytokines
SARS-CoV-2
COVID-19
title Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial Cells
title_full Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial Cells
title_fullStr Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial Cells
title_full_unstemmed Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial Cells
title_short Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium <i>Fusobacterium nucleatum</i> in Human Respiratory Epithelial Cells
title_sort expression of the sars cov 2 receptor ace2 and proinflammatory cytokines induced by the periodontopathic bacterium i fusobacterium nucleatum i in human respiratory epithelial cells
topic ACE2
periodontitis
<i>Fusobacterium nucleatum</i>
proinflammatory cytokines
SARS-CoV-2
COVID-19
url https://www.mdpi.com/1422-0067/22/3/1352
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