Allicin May Promote Reversal of T-Cell Dysfunction in Periodontitis via the PD-1 Pathway

Int J Mol Sci. 2021 Aug 25;22(17):9162. doi: 10.3390/ijms22179162.

Abstract

We evaluated the role of allicin in periodontitis using an in silico and in vitro design. An in silico docking analysis was performed to assess the plausible interactions between allicin and PD-L1. The cytokine profile of gingival crevicular fluid (GCF) samples obtained from periodontitis patients was estimated by cytometric bead array. CD3+ lymphocytes isolated from the peripheral blood were sorted and characterized using immunomagnetic techniques. Cultured and expanded lymphocytes were treated with the GCF samples to induce T-cell exhaustion. Optimum concentrations of allicin were added to exhausted lymphocytes to compare the expression of TIM-3 and LAG-3 gene expression at baseline and post-treatment. Allicin was found to bind to the PD-L1 molecule as revealed by the in-silico experiment, which is possibly an inhibitory interaction although not proven. GCF from periodontitis patients had significantly higher concentrations of TNF-α, CCL2, IL-6, IFN-γ, and CXCL8 than controls. GCF treatment of CD3+ lymphocytes from the periodontitis patients significantly increased expression of T-cell exhaustion markers TIM-3 and LAG-3. Allicin administration with GCF treatment resulted in significant lowering of the expression of exhaustion markers. Allicin may exert an immunostimulatory role and reverse immune-destructive mechanisms such as T-cell exhaustion.

Keywords: T lymphocytes; allicin; gingival crevicular fluid; periodontitis.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • B7-H1 Antigen / chemistry
  • B7-H1 Antigen / metabolism*
  • Binding Sites
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL6 / genetics
  • Chemokine CXCL6 / metabolism
  • Disulfides / chemistry
  • Disulfides / pharmacology*
  • Hepatitis A Virus Cellular Receptor 2 / genetics
  • Hepatitis A Virus Cellular Receptor 2 / metabolism
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lymphocyte Activation Gene 3 Protein
  • Periodontitis / metabolism*
  • Protein Binding
  • Sulfinic Acids / chemistry
  • Sulfinic Acids / pharmacology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CCL2 protein, human
  • CD274 protein, human
  • CXCL6 protein, human
  • Chemokine CCL2
  • Chemokine CXCL6
  • Disulfides
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Interleukin-6
  • Sulfinic Acids
  • Tumor Necrosis Factor-alpha
  • allicin
  • Interferon-gamma
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human