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The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0001-7105-0425
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, 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 5, p. 361-375Article in journal (Refereed) Published
Abstract [en]

Neutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps (NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram-negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild-type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild-type strain ATCC33277, whereas the other wild-type strain W50 was less effective. Quantitative real-time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P.gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P.gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria.

Place, publisher, year, edition, pages
2015. Vol. 30, no 5, p. 361-375
Keywords [en]
neutrophils, neutrophil extracellular traps, periodontitis, phagocytosis, reactive oxygen species
National Category
Dentistry
Identifiers
URN: urn:nbn:se:oru:diva-46034DOI: 10.1111/omi.12099ISI: 000361007200003PubMedID: 25869817Scopus ID: 2-s2.0-84941023684OAI: oai:DiVA.org:oru-46034DiVA, id: diva2:859446
Funder
Swedish Heart Lung FoundationSwedish Research Council
Note

Funding Agency:

Foundation of Olle Engkvist

Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2017-12-01Bibliographically approved
In thesis
1. Monocyte and Neutrophil Inflammatory Responses to the Periodontopathogen Porphyromonas gingivalis
Open this publication in new window or tab >>Monocyte and Neutrophil Inflammatory Responses to the Periodontopathogen Porphyromonas gingivalis
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Periodontitis is one of the most common adult infections. Duing bacteremia in healthy individuals or patients with chronic periodontitis, a number of oral bacteria such as Porphyromonas gingivalis encounter inflammatory cells in the blood eg. platelets, neutrophils and monocytes. Although several studies have suggested an association between periodontitis and cardiovascular diseases, the infection and inflammatory mechanisms are poorly understood. Hence, the aim of this thesis was to elucidate the mechanisms that are involved in P. gingivalis interaction with blood leukocytes, in order to further understand the molecular pathogenesis that renders periodontitis as a risk factor for several systemic conditions. We have demonstrated that P. gingivalis induces ROS production in neutrophils, THP1 cells and in whole blood, through activation of pattern recognition receptors, such as toll-like receptors, nuclear oligomerizing domains and protease- activated receptors. Besides, we have also shown that monocytes secrete IL-1β and CXCL8 in response to P. gingivalis. Both these cytokines prime neutrophils, endothelial cells and other vascular cells in an autocrine and paracrine manner. P. gingivalis has a plethora of virulence factors of which gingipains are very unique. In addition to activating inflammatory signalling pathways in cells, gingipains also regulate CXCL8 and IL-1β, thereby curtailing the host defence strategies. We demonstrated that oxidized LDL, but not native LDL, induces IL-1β release and CD36 expression on THP1 cells. Furthermore, LDL mildly modifies P. gingivalis-induced inflammatory responses as well as CD36 expression in THP1 cells. We also observed that P. gingivalis is eliminated mainly by phagocytosis in neutrophils. In summary, these studies clarify the mechanisms of interaction between P. gingivalis and leukocytes, which can increase the understanding of the pathogenesis of periodontitis and associated systemic disorders.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2016. p. 63
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 138
Keywords
Monocytes, Neutrophils, Porphyromonas gingivalis, Gingipains
National Category
Other Basic Medicine
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-48228 (URN)978-91-7529-122-2 (ISBN)
Public defence
2016-04-15, Universitetssjukhuset, hörsal C2, Södra Grev Rosengatan, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2016-02-12 Created: 2016-02-12 Last updated: 2018-01-10Bibliographically approved

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Jayaprakash, KartheyaeneDemirel, IsakKhalaf, HazemBengtsson, Torbjörn

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Molecular Oral Microbiology
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