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The role of Porphyromonas gingivalis gingipains in platelet activation and innate immune modulation
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Department of Clinical Pathology and Clinical Genetics, Linköping University Hospital, Linköping, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden.
2015 (English)In: Molecular Oral Microbiology, ISSN 2041-1006, E-ISSN 2041-1014, Vol. 30, no 1, p. 62-73Article in journal (Refereed) Published
Abstract [en]

Platelets are considered to have important functions in inflammatory processes and as actors in the innate immunity. Several studies have shown associations between cardiovascular disease and periodontitis, where the oral anaerobic pathogen Porphyromonas gingivalis has a prominent role in modulating the immune response. Porphyromonas gingivalis has been found in atherosclerotic plaques, indicating spreading of the pathogen via the circulation, with an ability to interact with and activate platelets via e.g. Toll-like receptors (TLR) and protease-activated receptors. We aimed to evaluate how the cysteine proteases, gingipains, of P.gingivalis affect platelets in terms of activation and chemokine secretion, and to further investigate the mechanisms of platelet-bacteria interaction. This study shows that primary features of platelet activation, i.e. changes in intracellular free calcium and aggregation, are affected by P.gingivalis and that arg-gingipains are of great importance for the ability of the bacterium to activate platelets. The P.gingivalis induced a release of the chemokine RANTES, however, to a much lower extent compared with the TLR2/1-agonist Pam(3)CSK(4), which evoked a time-dependent release of the chemokine. Interestingly, the TLR2/1-evoked response was abolished by a following addition of viable P.gingivalis wild-types and gingipain mutants, showing that both Rgp and Kgp cleave the secreted chemokine. We also demonstrate that Pam(3)CSK(4)-stimulated platelets release migration inhibitory factor and plasminogen activator inhibitor-1, and that also these responses were antagonized by P.gingivalis. These results supports immune-modulatory activities of P.gingivalis and further clarify platelets as active players in innate immunity and in sensing bacterial infections, and as target cells in inflammatory reactions induced by P.gingivalis infection.

Place, publisher, year, edition, pages
2015. Vol. 30, no 1, p. 62-73
Keywords [en]
gingipains, migration inhibitory factor, periodontitis, platelets, Porphyromonas gingivalis, RANTES
National Category
Microbiology in the medical area Medical and Health Sciences
Research subject
Microbiology
Identifiers
URN: urn:nbn:se:oru:diva-42616DOI: 10.1111/omi.12067ISI: 000347897100006PubMedID: 25043711Scopus ID: 2-s2.0-84920994869OAI: oai:DiVA.org:oru-42616DiVA, id: diva2:788227
Funder
Swedish Heart Lung FoundationSwedish Research Council
Note

Funding Agency:

Foundation of Olle Engkvist

Available from: 2015-02-13 Created: 2015-02-13 Last updated: 2018-01-11Bibliographically approved
In thesis
1. Platelets as immune cells in sensing bacterial infection
Open this publication in new window or tab >>Platelets as immune cells in sensing bacterial infection
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university, 2015. p. 78
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 116
Keywords
Platelets, infection, TLR2/1, Porphyromonas gingivalis, inflammatory mediators, lipid peroxidation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Cell Research
Identifiers
urn:nbn:se:oru:diva-40397 (URN)978-91-7529-060-7 (ISBN)
Public defence
2015-03-06, Universitetssjukhuset, Wilandersalen, Södra Grev Rosengatan, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-01-08 Created: 2015-01-08 Last updated: 2017-10-17Bibliographically approved

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Klarström-Engström, KristinKhalaf, HazemBengtsson, Torbjörn

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School of Health and Medical Sciences, Örebro University, SwedenSchool of Medicine, Örebro University, Sweden
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Molecular Oral Microbiology
Microbiology in the medical areaMedical and Health Sciences

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