Porphyromonas gingivalis affects neutrophil pro-inflammatory activities

Porphyromonas gingivalis is the primary pathogen responsible for the development of periodontal inflammatory disease. Although gingipains are the major virulence factor of the pathogen, their role in impairing apoptosis and immune cell function is not fully understood. To investigate the impact of g...

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Main Authors: Agnieszka Zimny, Alicja Płonczyńska, Wiktor Jakubowski, Natalia Zubrzycka, Jan Potempa, Maja Sochalska
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1419651/full
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author Agnieszka Zimny
Alicja Płonczyńska
Alicja Płonczyńska
Wiktor Jakubowski
Natalia Zubrzycka
Natalia Zubrzycka
Jan Potempa
Jan Potempa
Maja Sochalska
author_facet Agnieszka Zimny
Alicja Płonczyńska
Alicja Płonczyńska
Wiktor Jakubowski
Natalia Zubrzycka
Natalia Zubrzycka
Jan Potempa
Jan Potempa
Maja Sochalska
author_sort Agnieszka Zimny
collection DOAJ
description Porphyromonas gingivalis is the primary pathogen responsible for the development of periodontal inflammatory disease. Although gingipains are the major virulence factor of the pathogen, their role in impairing apoptosis and immune cell function is not fully understood. To investigate the impact of gingipains on neutrophil viability and function, we conducted studies using murine HoxB8 neutrophils and primary human neutrophils infected with wild-type strains of Porphyromonas gingivalis (W83 and ATCC 33277), or a gingipains-null mutant with deleted gingipains encoding genes, or wild-type bacteria preincubated with specific gingipain inhibitors. Flow cytometry revealed that wild-type Porphyromonas gingivalis had a marked effect on neutrophil viability regulated by anti-apoptotic proteins belonging to the Bcl-2 family; however, these effects were independent of gingipain expression or activity. Importantly, experiments using primary human neutrophils and macrophages revealed that gingipains play a significant role in the disruption of immune cell functions via the induction of reactive oxygen species and inactivation of neutrophil elastase activity. Additionally, although gingipains played a role in modulating the IL-8-dependent inflammatory response of human neutrophils, they did not affect the expression levels of pro-inflammatory cytokines TNF-α and IL-6.
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institution Kabale University
issn 2296-634X
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publisher Frontiers Media S.A.
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spelling doaj-art-edd4a4d757f34e61953bc3a8064b04802025-01-28T06:41:27ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.14196511419651Porphyromonas gingivalis affects neutrophil pro-inflammatory activitiesAgnieszka Zimny0Alicja Płonczyńska1Alicja Płonczyńska2Wiktor Jakubowski3Natalia Zubrzycka4Natalia Zubrzycka5Jan Potempa6Jan Potempa7Maja Sochalska8Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandDepartment of Oral Immunity and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United StatesDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandPorphyromonas gingivalis is the primary pathogen responsible for the development of periodontal inflammatory disease. Although gingipains are the major virulence factor of the pathogen, their role in impairing apoptosis and immune cell function is not fully understood. To investigate the impact of gingipains on neutrophil viability and function, we conducted studies using murine HoxB8 neutrophils and primary human neutrophils infected with wild-type strains of Porphyromonas gingivalis (W83 and ATCC 33277), or a gingipains-null mutant with deleted gingipains encoding genes, or wild-type bacteria preincubated with specific gingipain inhibitors. Flow cytometry revealed that wild-type Porphyromonas gingivalis had a marked effect on neutrophil viability regulated by anti-apoptotic proteins belonging to the Bcl-2 family; however, these effects were independent of gingipain expression or activity. Importantly, experiments using primary human neutrophils and macrophages revealed that gingipains play a significant role in the disruption of immune cell functions via the induction of reactive oxygen species and inactivation of neutrophil elastase activity. Additionally, although gingipains played a role in modulating the IL-8-dependent inflammatory response of human neutrophils, they did not affect the expression levels of pro-inflammatory cytokines TNF-α and IL-6.https://www.frontiersin.org/articles/10.3389/fcell.2025.1419651/fullporphyromonas gingivalisgingipainsBcl-2 family proteinsapoptosisneutrophilsmacrophages
spellingShingle Agnieszka Zimny
Alicja Płonczyńska
Alicja Płonczyńska
Wiktor Jakubowski
Natalia Zubrzycka
Natalia Zubrzycka
Jan Potempa
Jan Potempa
Maja Sochalska
Porphyromonas gingivalis affects neutrophil pro-inflammatory activities
Frontiers in Cell and Developmental Biology
porphyromonas gingivalis
gingipains
Bcl-2 family proteins
apoptosis
neutrophils
macrophages
title Porphyromonas gingivalis affects neutrophil pro-inflammatory activities
title_full Porphyromonas gingivalis affects neutrophil pro-inflammatory activities
title_fullStr Porphyromonas gingivalis affects neutrophil pro-inflammatory activities
title_full_unstemmed Porphyromonas gingivalis affects neutrophil pro-inflammatory activities
title_short Porphyromonas gingivalis affects neutrophil pro-inflammatory activities
title_sort porphyromonas gingivalis affects neutrophil pro inflammatory activities
topic porphyromonas gingivalis
gingipains
Bcl-2 family proteins
apoptosis
neutrophils
macrophages
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1419651/full
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AT wiktorjakubowski porphyromonasgingivalisaffectsneutrophilproinflammatoryactivities
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