The role of Porphyromonas gingivalis gingipains in platelet activation and innate immune modulation
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
2015-02-132015-02-132018-01-11Bibliographically approved
In thesis