Serotype b of Aggregatibacter actinomycetemcomitans increases osteoclast and memory T-lymphocyte activation

• Published in: Molecular oral microbiology Vol. 31; no. 2; pp. 162 - 174
• Main Authors: Melgar-Rodríguez, S., Díaz-Zúñiga, J., Alvarez, C., Rojas, L., Monasterio, G., Carvajal, P., Escobar, A., Sanz, M., Vernal, R.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.04.2016; Wiley Subscription Services, Inc
• Subjects: Aggregatibacter actinomycetemcomitans; Aggregatibacter actinomycetemcomitans - immunology; Antigens, Bacterial - immunology; Antigens, Bacterial - pharmacology; bone resorption; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - microbiology; Cell Differentiation - immunology; Chronic Periodontitis - immunology; Chronic Periodontitis - microbiology; Dendritic Cells - immunology; Forkhead Transcription Factors - biosynthesis; GATA3 Transcription Factor - biosynthesis; Humans; Immunologic Memory - immunology; Lipopolysaccharides - pharmacology; Lymphocyte Activation; Lymphocytes; Nuclear Receptor Subfamily 1, Group F, Member 3 - biosynthesis; osteoclasts; Osteoclasts - immunology; periodontitis; RANK ligand; RANK Ligand - immunology; Serogroup; T lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes - microbiology; T lymphocytes; Aggregatibacter actinomycetemcomitans; RANK ligand; bone resorption; osteoclasts; periodontitis
• ISSN: 2041-1006; 2041-1014; 2041-1014
• DOI: 10.1111/omi.12112

Summary 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.