IADR Abstract Archives
Hyaluronan Fragments Enhance the Dendritic Cells/T-lymphocyte Response Against Periodonto-pathogens
Objectives: Periodontitis are chronic immuno-inflammatory diseases elicited by periodonto-pathogen bacteria, such as Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, and characterized by tooth-supporting tissues destruction. A. actinomycetemcomitans serotype b and P. gingivalis serotype K1 have been described as the most immunogenic serotypes. Tissue destruction mainly affects extracellular matrix (ECM) components such as Hyaluronan, and evidence demonstrates that low-molecular-weight-Hyaluronan (LMW-HA) fragments have immunogenicity as damage-associated-molecular-pattern (DAMP) through stimulation of dendritic cells (DCs) and T-lymphocytes. This study aimed to analyze the potential of LMW-HA to enhance the immuno-inflammatory response of DCs and naive Th-lymphocytes against A. actinomycetemcomitans serotype b or P. gingivalis serotype K1, and to determine the LMW-HA levels in periodontitis patients.
Methods: Two groups of LMW-HA-pulsed/non-pulsed DCs were infected with A. actinomycetemcomitans serotype b or P. gingivalis serotype K1 and the mRNA cytokine expression (IL-1β/IL-6/IL-12/IL-23/TNF-α) was quantified by qPCR. Afterward, the previously LMW-HA-pulsed/non-pulsed infected DCs were co-cultured with two groups of LMW-HA-pulsed/non-pulsed naive T-helper (Th) lymphocytes, and the master-switch transcription factor gene/signature cytokine mRNA expression (T-bet/IFN-γ, RORC2/IL-17, and AhR/IL-22) was determined by qPCR. In addition, gingival crevicular fluid samples of healthy subjects and periodontitis patients (pre/post treatment) were collected and total LMW-HA levels were quantified by ELISA.
Results: Higher levels of LMW-HA were detected in periodontitis patients compared with healthy subjects. In addition, higher expression levels of IL-1β/IL-6/IL-12/IL-23/TNF-α were detected in LMW-HA-pulsed P. gingivalis/A. actinomycetemcomitans-infected DCs as compared with non-pulsed. Correspondingly, T-bet/IFN-γ, RORC2/IL-17, and AhR/IL-22 expression levels were increased in LMW-HA-pulsed naive T-helper lymphocytes in comparison with non-pulsed.
Conclusions: These data demonstrate that Hyaluronan fragments were increased during periodontitis, even after treatment. Furthermore, these fragments induced a stronger DCs/Th-lymphocytes response against P. gingivalis or A. actinomycetemcomitans infection.
Methods: Two groups of LMW-HA-pulsed/non-pulsed DCs were infected with A. actinomycetemcomitans serotype b or P. gingivalis serotype K1 and the mRNA cytokine expression (IL-1β/IL-6/IL-12/IL-23/TNF-α) was quantified by qPCR. Afterward, the previously LMW-HA-pulsed/non-pulsed infected DCs were co-cultured with two groups of LMW-HA-pulsed/non-pulsed naive T-helper (Th) lymphocytes, and the master-switch transcription factor gene/signature cytokine mRNA expression (T-bet/IFN-γ, RORC2/IL-17, and AhR/IL-22) was determined by qPCR. In addition, gingival crevicular fluid samples of healthy subjects and periodontitis patients (pre/post treatment) were collected and total LMW-HA levels were quantified by ELISA.
Results: Higher levels of LMW-HA were detected in periodontitis patients compared with healthy subjects. In addition, higher expression levels of IL-1β/IL-6/IL-12/IL-23/TNF-α were detected in LMW-HA-pulsed P. gingivalis/A. actinomycetemcomitans-infected DCs as compared with non-pulsed. Correspondingly, T-bet/IFN-γ, RORC2/IL-17, and AhR/IL-22 expression levels were increased in LMW-HA-pulsed naive T-helper lymphocytes in comparison with non-pulsed.
Conclusions: These data demonstrate that Hyaluronan fragments were increased during periodontitis, even after treatment. Furthermore, these fragments induced a stronger DCs/Th-lymphocytes response against P. gingivalis or A. actinomycetemcomitans infection.