Science and Research

Porphyromonas gingivalis Cell Wall Components Induce Programmed Death Ligand 1 (PD-L1) Expression on Human Oral Carcinoma Cells by a Receptor-Interacting Protein Kinase 2 (RIP2)-Dependent Mechanism

Programmed death-ligand 1 (PD-L1/B7-H1) serves as a cosignaling molecule in cell-mediated immune responses and contributes to chronicity of inflammation and the escape of tumor cells from immunosurveillance. Here, we investigated the molecular mechanisms leading to PD-L1 upregulation in human oral carcinoma cells and in primary human gingival keratinocytes in response to infection with Porphyromonas gingivalis (P. gingivalis), a keystone pathogen for the development of periodontitis. The bacterial cell wall component peptidoglycan uses bacterial outer membrane vesicles to be taken up by cells. Internalized peptidoglycan triggers cytosolic receptors to induce PD-L1 expression in a myeloid differentiation primary response 88 (Myd88)-independent and receptor-interacting serine/threonine-protein kinase 2 (RIP2)-dependent fashion. Interference with the kinase activity of RIP2 or mitogen-activated protein (MAP) kinases interferes with inducible PD-L1 expression.

  • Groeger, S.
  • Denter, F.
  • Lochnit, G.
  • Schmitz, M. L.
  • Meyle, J.

Keywords

  • Adaptor Proteins, Signal Transducing/metabolism
  • B7-H1 Antigen/*metabolism
  • Bacteroidaceae Infections/*metabolism/microbiology
  • Carcinoma/*metabolism/microbiology
  • Cell Line, Tumor
  • Cell Wall/*metabolism
  • Gingiva/metabolism/microbiology
  • Humans
  • Keratinocytes/metabolism/microbiology
  • Mitogen-Activated Protein Kinases/metabolism
  • Mouth Neoplasms/*metabolism/microbiology
  • Periodontitis/metabolism/microbiology
  • Porphyromonas gingivalis/*metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinase 2/*metabolism
  • Up-Regulation/physiology
  • *b7-h1
  • *pd-l1
  • *Porphyromonas gingivalis
  • *immune evasion
  • *immune suppression
  • *signaling pathway
Publication details
DOI: 10.1128/iai.00051-20
Journal: Infect Immun
Number: 5
Work Type: Original
Location: UGMLC
Disease Area: PH
Partner / Member: JLU
Access-Number: 32041789

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