<i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis
Periodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with periodontitis, <i>Porphyromonas gingivalis</i> has been identified as a keystone pathogen. The immune-modulatory functi...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12922 |
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| author | Zsombor Prucsi Agnieszka Zimny Alicja Płonczyńska Natalia Zubrzycka Jan Potempa Maja Sochalska |
| author_facet | Zsombor Prucsi Agnieszka Zimny Alicja Płonczyńska Natalia Zubrzycka Jan Potempa Maja Sochalska |
| author_sort | Zsombor Prucsi |
| collection | DOAJ |
| description | Periodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with periodontitis, <i>Porphyromonas gingivalis</i> has been identified as a keystone pathogen. The immune-modulatory function of <i>P. gingivalis</i> is well characterized, but the mechanism by which this bacterium secretes peptidyl arginine deiminase (PPAD), a protein/peptide citrullinating enzyme, thus contributing to the infinite feed-forward loop of inflammation, is not fully understood. To determine the functional role of citrullination in periodontitis, neutrophils were stimulated by <i>P. gingivalis</i> bearing wild-type PPAD and by a PPAD mutant strain lacking an active enzyme. Flow cytometry showed that PPAD contributed to prolonged neutrophil survival upon bacterial stimulation, accompanied by the secretion of aberrant IL-6 and TNF-α. To further assess the complex mechanism by which citrullination sustains a chronic inflammatory state, the ROS production and phagocytic activity of neutrophils were evaluated. Flow cytometry and colony formation assays showed that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines, while enhancing the resilience of the bacteria to phagocytosis. |
| first_indexed | 2024-03-10T23:52:42Z |
| format | Article |
| id | doaj.art-c5b39cd68b9f436989b58883ab7c2fbb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:52:42Z |
| publishDate | 2023-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c5b39cd68b9f436989b58883ab7c2fbb2023-11-19T01:32:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161292210.3390/ijms241612922<i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in PeriodontitisZsombor Prucsi0Agnieszka Zimny1Alicja Płonczyńska2Natalia Zubrzycka3Jan Potempa4Maja Sochalska5Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, PolandPeriodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with periodontitis, <i>Porphyromonas gingivalis</i> has been identified as a keystone pathogen. The immune-modulatory function of <i>P. gingivalis</i> is well characterized, but the mechanism by which this bacterium secretes peptidyl arginine deiminase (PPAD), a protein/peptide citrullinating enzyme, thus contributing to the infinite feed-forward loop of inflammation, is not fully understood. To determine the functional role of citrullination in periodontitis, neutrophils were stimulated by <i>P. gingivalis</i> bearing wild-type PPAD and by a PPAD mutant strain lacking an active enzyme. Flow cytometry showed that PPAD contributed to prolonged neutrophil survival upon bacterial stimulation, accompanied by the secretion of aberrant IL-6 and TNF-α. To further assess the complex mechanism by which citrullination sustains a chronic inflammatory state, the ROS production and phagocytic activity of neutrophils were evaluated. Flow cytometry and colony formation assays showed that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines, while enhancing the resilience of the bacteria to phagocytosis.https://www.mdpi.com/1422-0067/24/16/12922periodontitis<i>Porphyromonas gingivalis</i>Bcl-2 familyapoptosisneutrophils |
| spellingShingle | Zsombor Prucsi Agnieszka Zimny Alicja Płonczyńska Natalia Zubrzycka Jan Potempa Maja Sochalska <i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis International Journal of Molecular Sciences periodontitis <i>Porphyromonas gingivalis</i> Bcl-2 family apoptosis neutrophils |
| title | <i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis |
| title_full | <i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis |
| title_fullStr | <i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis |
| title_full_unstemmed | <i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis |
| title_short | <i>Porphyromonas gingivalis</i> Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis |
| title_sort | i porphyromonas gingivalis i peptidyl arginine deiminase ppad in the context of the feed forward loop of inflammation in periodontitis |
| topic | periodontitis <i>Porphyromonas gingivalis</i> Bcl-2 family apoptosis neutrophils |
| url | https://www.mdpi.com/1422-0067/24/16/12922 |
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