Activation of RANKL-induced osteoclasts and memory T lymphocytes by Porphyromonas gingivalis is serotype dependant.
OBJECTIVE
Destructive periodontitis is associated with a Th1-Th17 immune response and activation of RANKL-induced osteoclasts. In addition, Porphyromonas gingivalis K1 and K2 serotypes induce a strong Th1-Th17 response. This study aimed to investigate whether these P. gingivalis serotypes induce higher osteoclasts activation, by increased Th17-associated RANKL production, and an antigen-specific memory T-lymphocyte response.


METHODS
The RANKL production and TRAP(+) osteoclast induction were quantified on naïve T lymphocytes stimulated with dendritic cells primed with the P. gingivalis serotypes. The T-bet, GATA-3, RORC2 and Foxp3 expression was correlated with RANKL production. The frequency of proliferating memory T lymphocytes in response to P. gingivalis serotypes was determined in both periodontitis and healthy subjects.


RESULTS
T lymphocytes stimulated by K1 or K2-primed dendritic cells elicited higher levels of RANKL and TRAP(+) osteoclasts than cells stimulated with the other serotypes. RANKL positively correlated with RORC2. Whereas periodontitis patients had a higher frequency of memory T lymphocytes responding to K1 or K2, healthy subjects had a higher frequency of memory T lymphocytes responding to K4 or K(-) .


CONCLUSIONS
P. gingivalis serotypes K1 and K2, but not others, are associated with an increased production of the osteoclastogenesis-related factor RANKL. This important information suggests that these serotypes could elicit a greater bone resorption in vivo and have a role in the periodontitis pathogenesis.
Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain; Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago de Chile, Chile.
Rolando
R
Vernal
Jaime
J
Díaz-Zúñiga
Samanta
S
Melgar-Rodríguez
Myriam
M
Pujol
Eva
E
Diaz-Guerra
Augusto
A
Silva
Mariano
M
Sanz
Jose A
JA
Garcia-Sanz
D000135:Acid Phosphatase / Q000032:analysis / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D055113:Chronic Periodontitis / Q000276:immunology; D060966:Clonal Selection, Antigen-Mediated; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000032:analysis; D050990:GATA3 Transcription Factor / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007527:Isoenzymes / Q000032:analysis / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000032:analysis; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000145:classification / Q000276:immunology*; D053245:RANK Ligand / Q000032:analysis / Q000276:immunology*; D065288:Serogroup; D020825:T-Box Domain Proteins / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D000071681:Tartrate-Resistant Acid Phosphatase; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D000098815:T-bet Transcription Factor
D000942:Antigens, Bacterial; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007527:Isoenzymes; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053245:RANK Ligand; C539900:RORC protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C505688:TNFSF11 protein, human; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
Porphyromonas gingivalis; RANKL; T lymphocytes; bone resorption; periodontitis; serotypes