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Capsular-defective Porphyromonas gingivalis mutant strains induce less alveolar bone resorption than W50 wild-type strain due to a decreased Th1/Th17 immune response and less osteoclast activity

  • Gustavo Monasterio
    ,
  • Baltasar Fernández
    ,
  • Francisca Castillo
    ,
  • Carolina Rojas
    ,
  • ,
  • Leticia Rojas
*Corresponding author for this work
  • Universidad de Chile
    ,
  • ,
  • Pontificia Universidad Católica de Chile
    ,
  • Universidad Andrés Bello
    ,
  • Universidad Autónoma de Chile
Research Output:
Contribution to journal
Article
Peer-review

Publication Information

Output type

Research Output:
Contribution to journal
Article
Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 522-534 (13 pages)

Journal (Volume, Issue Number)

Journal of Periodontology (Volume 90, Issue 5)

Publication milestones

  • Published - 2019

Publication status

Published - 2019

ISSN

0022-3492

Publication IDs

  • Scopus: 85065949258
  • PubMed: 30397909

Abstract

Background: Encapsulation of Porphyromonas gingivalis has been demonstrated as responsible of several host immunological changes, which have been associated with the pathogenesis of periodontitis. Using a murine model of periodontitis and two isogenic non-capsulated mutants of P. gingivalis, this study aimed to analyze whether P. gingivalis encapsulation induces more severe alveolar bone resorption, and whether this bone loss is associated with a T-helper (Th)1 and Th17-pattern of immune response. Methods: Experimental periodontal infections were generated by oral inoculation with the encapsulated W50 wild-type strain or isogenic non-encapsulated ΔPG0116-PG0120 (GPA) and ΔPG0109-PG0118 (GPC) mutants of P. gingivalis. Periodontal infections induced with the encapsulated HG184 or non-encapsulated ATCC 33277 strains of P. gingivalis were used as controls. Alveolar bone resorption was analyzed using microcomputed tomography and scanning electron microscopy. The expression levels of Th1, Th2, Th17, or T regulatory-associated cytokines and RANKL, as well as the periodontal bacterial load, were quantified by quantitative polymerase chain reaction. The detection of Th1 and Th17 lymphocytes was analyzed by flow cytometry. Results: In the periodontal lesions, both capsular-defective knockout mutant strains of P. gingivalis induced less alveolar bone resorption than the encapsulated W50 wild-type strain. This decreased bone loss was associated with a dismissed RANKL expression, decreased Th1- and Th17-type of cytokine expression, reduced Th1 and Th17 lymphocyte detection, and low osteoclast finding. Conclusion: These data demonstrate that encapsulation of P. gingivalis plays a key role in the alveolar bone resorption induced during periodontitis, and this bone loss is associated with a Th1- and Th17-pattern of immune response triggered in the periodontal lesions.

Funding Details

We thank Dr. Arie Jan van Winkelhoff (University Medical Center Groningen, State University of Groningen, The Netherlands) and Drs. Michael A. Curtis and Joseph Aduse-Opoku (Queen Mary University of London, Barts, and The London School of Medicine and Dentistry, Centre for Immunology and Infectious Disease, Blizard Institute, London, UK) for providing us with the P. gingivalis wild-type and mutant strains. We are also grateful to Daniela Salinas and Darna Venegas (Microbiology Laboratory, Faculty of Dentistry, Universidad de Chile) for sharing their expertise on bacterial cultures. We thank the Experimental Platform Bio-CT, Faculty of Dentistry, Universidad de Chile (FONDEQUIP EQM150010) for performing the μCT analysis. This investigation has been supported by grants FONDECYT 1140904 and FONDECYT 1181780 from Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) from the Chilean Government. Gustavo Monasterio is a recipient of the fellowship CONICYT 21170297 from the Chilean Government. The authors report no conflicts of interest related to this study.
FundersFunding numbers
Blizard Institute
-
FONDEQUIP
EQM150010
Faculty of Dentistry, Universidad de Chile
-
London School of Medicine and Dentistry, Centre for Immunology and Infectious Disease
-
Microbiology Laboratory, Faculty of Dentistry, Universidad de Chile
-
State University of Groningen
-
QMUL
-
CONICYT
21170297
FONDECYT
1140904, 1181780