title: Serotype b of Aggregatibacter actinomycetemcomitans increases osteoclast and memory T-lymphocyte activation.
abstract: During periodontitis, alveolar bone resorption is associated with activation of T helper type 17 (Th17) lymphocytes and receptor activator of nuclear factor-κB ligand (RANKL) -induced osteoclasts. We previously reported that serotype b of Aggregatibacter actinomycetemcomitans has a higher capacity to trigger Th17-type differentiation and function in activated T lymphocytes and its lipopolysaccharide is a more potent immunogen compared with the other serotypes. This study aimed to investigate whether serotype b of A. actinomycetemcomitans induces higher Th17-associated RANKL production, RANKL-induced osteoclast activation, and antigen-specific memory T lymphocyte proliferation. On naive CD4(+) T lymphocytes stimulated with autologous dendritic cells primed with different A. actinomycetemcomitans serotypes, RANKL production, T-bet, GATA-3, RORC2 and Foxp3 expression, RORC2/RANKL intracellular double-expression, TRAP(+) osteoclast activation, and bone resorption were quantified. The frequency of proliferating memory T lymphocytes in response to A. actinomycetemcomitans serotypes was determined in periodontitis and healthy subjects. Naive CD4(+) T lymphocytes stimulated by serotype b-primed dendritic cells elicited higher levels of RANKL, RORC2, TRAP(+) osteoclasts, and bone resorption than the same cells stimulated with the other serotypes. RANKL positively correlated and co-expressed with RORC2. Memory T lymphocytes responding to serotype b were more frequently detected in periodontitis patients than healthy subjects. These results indicate that serotype b of A. actinomycetemcomitans is associated with higher production of RANKL and these increased levels are associated with Th17 lymphocyte induction, osteoclast activation, and bone resorption.
authors.affiliation: Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: S
authors.initials: S
authors.lastname: Melgar-Rodríguez
authors.affiliation: Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Zúñiga
authors.affiliation: Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Alvarez
authors.affiliation: Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Rojas
authors.affiliation: Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: G
authors.initials: G
authors.lastname: Monasterio
authors.affiliation: Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Carvajal
authors.affiliation: Dental Sciences Institute, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Escobar
authors.affiliation: Etiology and Therapy of Periodontal Diseases (ETEP) Research Group, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sanz
authors.affiliation: Periodontal Biology Laboratory, Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Vernal
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D055113:Chronic Periodontitis / Q000276:immunology / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D050990:GATA3 Transcription Factor / Q000096:biosynthesis; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis; D010010:Osteoclasts / Q000276:immunology*; D053245:RANK Ligand / Q000276:immunology; D065288:Serogroup; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D008070:Lipopolysaccharides; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053245:RANK Ligand; C539900:RORC protein, human; C505688:TNFSF11 protein, human
keywords: Aggregatibacter actinomycetemcomitans; RANK ligand; T lymphocytes; bone resorption; osteoclasts; periodontitis