B-cell cytokine responses to Porphyromonas gingivalis in patients with periodontitis and healthy controls

J Periodontol. 2023 Aug;94(8):997-1007. doi: 10.1002/JPER.22-0438. Epub 2023 Mar 5.

Abstract

Background: Cytokine-producing B cells play a well-established role in modifying immune responses in chronic inflammatory diseases. We characterized B-cell cytokine responses against periodontitis-associated bacteria in patients with periodontitis.

Methods: Blood and saliva samples were collected from patients with periodontitis grade B (N = 31) or grade C (N = 25), and 25 healthy controls (HCs). Mononuclear cells were stimulated with Porphyromonas gingivalis, Fusobacterium nucleatum, Staphylococcus epidermidis, or Cutibacterium acnes, and B-cell production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-10 and transforming growth factor (TGF)-β by B cells was assessed by flow cytometry.

Results: HCs had higher baseline frequencies of B cells producing IFN-γ or TNF-α than grade B patients, but only B cells from grade B patients showed significant differentiation into IFN-γ-, TNF-α-, TGF-β-, or IL-10-producing cells after challenge with P. gingivalis and into IFN-γ-, TGF-β-, or IL-10-producing cells after challenge F. nucleatum. Notably, the baseline frequency of IL-10-producing B cells from grade C patients correlated inversely with clinical attachment loss (AL). The major proportion of the IFN-γ- and TGF-β-producing B cells were CD27+ memory cells, while the IL-10-producing B cells were mainly CD27- CD5- .

Conclusions: B cells from grade B patients, particularly those harboring P. gingivalis, showed proinflammatory B-cell responses to P. gingivalis. Moreover, the baseline frequency of IL-10-producing B cells in the grade C group correlated inversely with AL, suggesting a diminished immunoregulatory capacity of IL-10-producing B cells in these patients.

Trial registration: ClinicalTrials.gov NCT03225950.

Keywords: B cells; Porphyromonas gingivalis; cytokines; periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines* / metabolism
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Periodontitis* / metabolism
  • Porphyromonas gingivalis / metabolism
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Interleukin-10
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Transforming Growth Factor beta

Associated data

  • ClinicalTrials.gov/NCT03225950