TY - JOUR

T1 - Cytokine responses of CD4+ T cells and NKT cells to periodontitis-associated bacteria in individuals with or without periodontitis

AU - Danielsen, Anne Katrine

AU - Massarenti, Laura

AU - Minculescu, Lia

AU - Jensen, Peter Østrup

AU - Hansen, Peter Riis

AU - Holmstrup, Palle

AU - Damgaard, Christian

AU - Nielsen, Claus Henrik

N1 - Publisher Copyright: © 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.

PY - 2024

Y1 - 2024

N2 - Aim: Periodontitis is an inflammatory disease driven by opportunistic bacteria including Porphyromonas gingivalis and Fusobacterium nucleatum, where T-cell and NKT-cell responses to these bacteria in patients with periodontitis grade B or C are not fully elucidated. The objective is to determine if exaggerated proinflammatory Th-cell responses to periodontitis-associated bacteria, but not commensal bacteria, is a characteristic of increased periodontitis grade. Methods: Mononuclear cells from patients with periodontitis grade C (n = 26) or grade B (n = 33) and healthy controls (HCs; n = 26) were stimulated with P. gingivalis, F. nucleatum or the commensal bacteria, Staphylococcus epidermidis and Cutibacterium acnes. Cytokine production by different T-cell populations and FOXP3-expression by regulatory T cells were assessed by flow cytometry. Results: Compared to HCs, grade C patients had decreased frequencies of interleukin (IL)-10-producing CD4+ T cells before stimulation (p =.02) and increased frequencies of IFN-y-producing CD4+ T cells after stimulation with P. gingivalis (p =.0019). Grade B patients had decreased frequencies of FOXP3+ CD4+ T cells before (p =.030) before and after stimulation with anti-CD2/anti-CD3/anti-CD28-loaded beads (p =.047), P. gingivalis (p =.013) and S. epidermidis (p =.018). Clinical attachment loss correlated with the frequencies of IFN-y-producing Th1 cells in P. gingivalis- and F. nucleatum-stimulated cultures in grade B patients (p =.023 and p =.048, respectively) and with the frequencies of Th17 cells in P. gingivalis-stimulated cultures (p =.0062) in grade C patients. Patients with periodontitis grade C or grade B showed lower frequencies of IL-10-producing NKT cells than HCs in unstimulated cultures (p =.0043 and p =.027 respectively). Conclusions: Both periodontitis groups showed decreased frequencies of immunoregulatory T-cell and NKT cell subsets at baseline. Clinical attachment loss correlated with P. gingivalis-induced Th17-responses in grade C patients and with Th1-responses in grade B patients when cells were stimulated with P. gingivalis, supporting that dysregulated pro-inflammatory T-cell responses to periodontitis-associated bacteria contribute to the pathogenesis of periodontitis.

AB - Aim: Periodontitis is an inflammatory disease driven by opportunistic bacteria including Porphyromonas gingivalis and Fusobacterium nucleatum, where T-cell and NKT-cell responses to these bacteria in patients with periodontitis grade B or C are not fully elucidated. The objective is to determine if exaggerated proinflammatory Th-cell responses to periodontitis-associated bacteria, but not commensal bacteria, is a characteristic of increased periodontitis grade. Methods: Mononuclear cells from patients with periodontitis grade C (n = 26) or grade B (n = 33) and healthy controls (HCs; n = 26) were stimulated with P. gingivalis, F. nucleatum or the commensal bacteria, Staphylococcus epidermidis and Cutibacterium acnes. Cytokine production by different T-cell populations and FOXP3-expression by regulatory T cells were assessed by flow cytometry. Results: Compared to HCs, grade C patients had decreased frequencies of interleukin (IL)-10-producing CD4+ T cells before stimulation (p =.02) and increased frequencies of IFN-y-producing CD4+ T cells after stimulation with P. gingivalis (p =.0019). Grade B patients had decreased frequencies of FOXP3+ CD4+ T cells before (p =.030) before and after stimulation with anti-CD2/anti-CD3/anti-CD28-loaded beads (p =.047), P. gingivalis (p =.013) and S. epidermidis (p =.018). Clinical attachment loss correlated with the frequencies of IFN-y-producing Th1 cells in P. gingivalis- and F. nucleatum-stimulated cultures in grade B patients (p =.023 and p =.048, respectively) and with the frequencies of Th17 cells in P. gingivalis-stimulated cultures (p =.0062) in grade C patients. Patients with periodontitis grade C or grade B showed lower frequencies of IL-10-producing NKT cells than HCs in unstimulated cultures (p =.0043 and p =.027 respectively). Conclusions: Both periodontitis groups showed decreased frequencies of immunoregulatory T-cell and NKT cell subsets at baseline. Clinical attachment loss correlated with P. gingivalis-induced Th17-responses in grade C patients and with Th1-responses in grade B patients when cells were stimulated with P. gingivalis, supporting that dysregulated pro-inflammatory T-cell responses to periodontitis-associated bacteria contribute to the pathogenesis of periodontitis.

KW - cytokines

KW - Fusobacterium Nucleatum

KW - NKT cells

KW - periodontitis

KW - Porphyromonas gingivalis

KW - T-helper cells

U2 - 10.1111/jre.13317

DO - 10.1111/jre.13317

M3 - Journal article

C2 - 38962877

AN - SCOPUS:85197422153

JO - Journal of Periodontal Research

JF - Journal of Periodontal Research

SN - 0022-3484

ER -