Metronidazole enhances killing of Porphyromonas gingivalis by human PMNs
Background and objectivesPeriodontitis affects the supporting structures of the teeth as a result of the interactions between the subgingival biofilm and the host immune system. Periodontal therapy in severe forms of periodontitis often utilizes antimicrobial agents with some potential to improve ho...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oral Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/froh.2022.933997/full |
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| author | Mihaela Anca Serbanescu Morvarid Oveisi Chunxiang Sun Noah Fine Anne Bosy Michael Glogauer Michael Glogauer |
| author_facet | Mihaela Anca Serbanescu Morvarid Oveisi Chunxiang Sun Noah Fine Anne Bosy Michael Glogauer Michael Glogauer |
| author_sort | Mihaela Anca Serbanescu |
| collection | DOAJ |
| description | Background and objectivesPeriodontitis affects the supporting structures of the teeth as a result of the interactions between the subgingival biofilm and the host immune system. Periodontal therapy in severe forms of periodontitis often utilizes antimicrobial agents with some potential to improve host defense responses. In the present study, we investigated the in vitro effect of metronidazole (MTZ) at concentrations achievable in the periodontal pocket on PMN activation and PMN mediated killing of Porphyromonas gingivalis.Materials and methodsFlow cytometry based assays were used to measure the impact of MTZ on PMN degranulation, neutrophil extracellular trap (NET) formation and myeloperoxidase (MPO) release and phagocytosis in response to the keystone oral pathogen P. gingivalis. Functional assays for PMN mediated killing of P. gingivalis and reactive oxygen species (ROS) production in PMN were also carried out.ResultsWe demonstrate that PMNs pretreated with MTZ (2 μg/ml or 50 μg/ml) displayed enhanced killing of P. gingivalis compared to untreated PMNs. At concentrations achieved physiologically in the periodontal pocket, MTZ induced PMN surface expression of two activation markers (CD66 and CD63). MTZ did not alter P. gingivalis-induced NETosis, but suppressed P. gingivalis-induced ROS production and phagocytosis.ConclusionMTZ displays a positive interaction with PMNs to potentiate PMN mediated killing of P. gingivalis and may therefore contribute to its beneficial effects in the treatment of periodontitis initiated by P. gingivalis infections including those refractory to conventional treatment. |
| first_indexed | 2024-04-14T02:18:09Z |
| format | Article |
| id | doaj.art-e4523d01268b4457a6ef3f10ed56fd5a |
| institution | Directory Open Access Journal |
| issn | 2673-4842 |
| language | English |
| last_indexed | 2024-04-14T02:18:09Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oral Health |
| spelling | doaj.art-e4523d01268b4457a6ef3f10ed56fd5a2022-12-22T02:18:07ZengFrontiers Media S.A.Frontiers in Oral Health2673-48422022-08-01310.3389/froh.2022.933997933997Metronidazole enhances killing of Porphyromonas gingivalis by human PMNsMihaela Anca Serbanescu0Morvarid Oveisi1Chunxiang Sun2Noah Fine3Anne Bosy4Michael Glogauer5Michael Glogauer6Faculty of Dentistry, University of Toronto, Toronto, ON, CanadaFaculty of Dentistry, University of Toronto, Toronto, ON, CanadaFaculty of Dentistry, University of Toronto, Toronto, ON, CanadaFaculty of Dentistry, University of Toronto, Toronto, ON, CanadaOraVital Inc., Toronto, ON, CanadaFaculty of Dentistry, University of Toronto, Toronto, ON, CanadaDepartment of Dental Oncology and Maxillofacial Prosthetics, Princess Margaret Cancer Centre, Toronto, ON, CanadaBackground and objectivesPeriodontitis affects the supporting structures of the teeth as a result of the interactions between the subgingival biofilm and the host immune system. Periodontal therapy in severe forms of periodontitis often utilizes antimicrobial agents with some potential to improve host defense responses. In the present study, we investigated the in vitro effect of metronidazole (MTZ) at concentrations achievable in the periodontal pocket on PMN activation and PMN mediated killing of Porphyromonas gingivalis.Materials and methodsFlow cytometry based assays were used to measure the impact of MTZ on PMN degranulation, neutrophil extracellular trap (NET) formation and myeloperoxidase (MPO) release and phagocytosis in response to the keystone oral pathogen P. gingivalis. Functional assays for PMN mediated killing of P. gingivalis and reactive oxygen species (ROS) production in PMN were also carried out.ResultsWe demonstrate that PMNs pretreated with MTZ (2 μg/ml or 50 μg/ml) displayed enhanced killing of P. gingivalis compared to untreated PMNs. At concentrations achieved physiologically in the periodontal pocket, MTZ induced PMN surface expression of two activation markers (CD66 and CD63). MTZ did not alter P. gingivalis-induced NETosis, but suppressed P. gingivalis-induced ROS production and phagocytosis.ConclusionMTZ displays a positive interaction with PMNs to potentiate PMN mediated killing of P. gingivalis and may therefore contribute to its beneficial effects in the treatment of periodontitis initiated by P. gingivalis infections including those refractory to conventional treatment.https://www.frontiersin.org/articles/10.3389/froh.2022.933997/fullmetronidazoleperiodontitisPorphyromonas gingivalisanti-infective agentsneutrophils (PMNs) |
| spellingShingle | Mihaela Anca Serbanescu Morvarid Oveisi Chunxiang Sun Noah Fine Anne Bosy Michael Glogauer Michael Glogauer Metronidazole enhances killing of Porphyromonas gingivalis by human PMNs Frontiers in Oral Health metronidazole periodontitis Porphyromonas gingivalis anti-infective agents neutrophils (PMNs) |
| title | Metronidazole enhances killing of Porphyromonas gingivalis by human PMNs |
| title_full | Metronidazole enhances killing of Porphyromonas gingivalis by human PMNs |
| title_fullStr | Metronidazole enhances killing of Porphyromonas gingivalis by human PMNs |
| title_full_unstemmed | Metronidazole enhances killing of Porphyromonas gingivalis by human PMNs |
| title_short | Metronidazole enhances killing of Porphyromonas gingivalis by human PMNs |
| title_sort | metronidazole enhances killing of porphyromonas gingivalis by human pmns |
| topic | metronidazole periodontitis Porphyromonas gingivalis anti-infective agents neutrophils (PMNs) |
| url | https://www.frontiersin.org/articles/10.3389/froh.2022.933997/full |
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