Differential Response of Human Dendritic Cells upon Stimulation with Encapsulated or Non-Encapsulated Isogenic Strains of Porphyromonas gingivalis

Int J Mol Sci. 2024 Apr 20;25(8):4510. doi: 10.3390/ijms25084510.

Abstract

During periodontitis, the extracellular capsule of Porphyromonas gingivalis favors alveolar bone loss by inducing Th1 and Th17 patterns of lymphocyte response in the infected periodontium. Dendritic cells recognize bacterial antigens and present them to T lymphocytes, defining their activation and polarization. Thus, dendritic cells could be involved in the Th1 and Th17 response induced against the P. gingivalis capsule. Herein, monocyte-derived dendritic cells were obtained from healthy individuals and then stimulated with different encapsulated strains of P. gingivalis or two non-encapsulated isogenic mutants. Dendritic cell differentiation and maturation were analyzed by flow cytometry. The mRNA expression levels for distinct Th1-, Th17-, or T-regulatory-related cytokines and transcription factors, as well as TLR2 and TLR4, were assessed by qPCR. In addition, the production of IL-1β, IL-6, IL-23, and TNF-α was analyzed by ELISA. The encapsulated strains and non-encapsulated mutants of P. gingivalis induced dendritic cell maturation to a similar extent; however, the pattern of dendritic cell response was different. In particular, the encapsulated strains of P. gingivalis induced higher expression of IRF4 and NOTCH2 and production of IL-1β, IL-6, IL-23, and TNF-α compared with the non-encapsulated mutants, and thus, they showed an increased capacity to trigger Th1 and Th17-type responses in human dendritic cells.

Keywords: Porphyromonas gingivalis; capsule; cytokines; dendritic cells; transcription factors.

MeSH terms

  • Bacterial Capsules / immunology
  • Bacterial Capsules / metabolism
  • Bacteroidaceae Infections / immunology
  • Bacteroidaceae Infections / microbiology
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines* / metabolism
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • Dendritic Cells* / microbiology
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Porphyromonas gingivalis* / immunology
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism
  • Th1 Cells / immunology
  • Th17 Cells* / immunology
  • Th17 Cells* / metabolism
  • Toll-Like Receptor 2* / genetics
  • Toll-Like Receptor 2* / metabolism
  • Toll-Like Receptor 4* / genetics
  • Toll-Like Receptor 4* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Cytokines
  • TLR2 protein, human
  • interferon regulatory factor-4
  • Interferon Regulatory Factors
  • Receptor, Notch2
  • TLR4 protein, human
  • Tumor Necrosis Factor-alpha