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Although multiple species and risk factors are associated with periodontitis, Porphyromonas gingivalis has been identified as a keystone pathogen. The immune-modulatory function of P.\u00a0gingivalis 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 P.\u00a0gingivalis 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-\u03b1. 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.<\/jats:p>","DOI":"10.3390\/ijms241612922","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T10:14:38Z","timestamp":1692353678000},"page":"12922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Porphyromonas gingivalis Peptidyl Arginine Deiminase (PPAD) in the Context of the Feed-Forward Loop of Inflammation in Periodontitis"],"prefix":"10.3390","volume":"24","author":[{"given":"Zsombor","family":"Prucsi","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Zimny","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"P\u0142onczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"},{"name":"Doctoral School of Exact and Natural Sciences, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-706X","authenticated-orcid":false,"given":"Natalia","family":"Zubrzycka","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"},{"name":"Doctoral School of Exact and Natural Sciences, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3600-7461","authenticated-orcid":false,"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"},{"name":"Department of Oral Immunity and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6665-3309","authenticated-orcid":false,"given":"Maja","family":"Sochalska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"ref_1","unstructured":"(2021, March 23). 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