4.4 Article

T-lymphocyte phenotype and function triggered by Aggregatibacter actinomycetemcomitans is serotype-dependent

Journal

JOURNAL OF PERIODONTAL RESEARCH
Volume 50, Issue 6, Pages 824-835

Publisher

WILEY
DOI: 10.1111/jre.12270

Keywords

Aggregatibacter actinomycetemcomitans; cytokines; lipopolysaccharide; serotypes; T lymphocytes; transcription factors

Funding

  1. Dental School of Universidad de Chile [FIOUCh 09-8]
  2. Chilean Government [FONDECYT 11100298, 1140904]

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Background and ObjectiveBased on lipopolysaccharide (LPS) antigenicity, different Aggregatibacter actinomycetemcomitans serotypes have been described. Serotype b strains have demonstrated a stronger capacity to trigger cytokine production on dendritic cells (DCs). As DCs regulate the development of T-lymphocyte lineages, the objective of this investigation was to study the response of T lymphocytes after being stimulated with autologous DCs primed with different bacterial strains belonging to the most prevalent serotypes of A.actinomycetemcomitans in humans: a-c. Material and MethodsHuman DCs were primed with increasing multiplicity of infection (10(-1)-10(2)) or the purified LPS (10-50ng/mL) of A.actinomycetemcomitans serotypes a-c and then used to stimulate autologous naive CD4(+) T lymphocytes. The T-helper (Th) type 1, Th2, Th17 and T-regulatory transcription factors T-bet, GATA-3, RORC2 and Foxp3, which are the master-switch genes implied in their specific differentiation, as well as T-cell phenotype-specific cytokine patterns were quantified by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, the intracellular expression of T-bet/interferon-, GATA-3/interleukin-4, RORC2/interleukin-17A and Foxp3/transforming growth factor-1 was analysed by double staining and flow cytometry. ResultsAll the A.actinomycetemcomitans serotypes led to T-lymphocyte activation; however, when T lymphocytes were stimulated with DCs primed with the A.actinomycetemcomitans serotype b strain or their purified LPS, higher levels of Th1- and Th17-associated transcription factors and cytokines were detected compared with similar experiments with the other serotypes. ConclusionThese results demonstrate that serotype b of A.actinomycetemcomitans has a higher capacity of trigger Th1 and Th17 phenotype and function and it was demonstrated that their LPS is a more potent immunogen compared with the other serotypes.

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