Subcutaneous vaccination with Porphyromonas gingivalis ameliorates periodontitis by modulating Th17/Treg imbalance in a murine model

Wang, Linyuan; Guan, Naifu; Jin, Ying; Lin, Xiaoping; Gao, Hong

doi:10.1016/j.intimp.2015.01.007

Cited by 42 publications

(59 citation statements)

References 47 publications

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“…They reported that the expression levels of TGFβ-1 and IL-10 mRNA were significantly increased ( p <0.01) implying an adverse role of these cytokines in modulating Th17/Treg imbalance. Furthermore, in the spleen, the ratio and number of Treg cells were significantly diminished ( p <0.05) supporting an immunosuppressive role of these cytokines in their clonal expansion (48). Accordingly, Th17 and Treg cells may be used to clarify the role of adaptive immune responses in periodontal disease instead of the originally proposed Th1/Th2 model (19).…”

Section: T Cellsmentioning

confidence: 85%

“…The results demonstrated that the vaccination inhibited the Th17 cell response and increased the Treg cell response affording protection to the mice from alveolar bone resorption and inflammation (48). Similar results were obtained in the in vivo experiment with all- trans retinoic acid (ATRA) administration which modulated the Th17/Treg imbalance and protected against experimental periodontitis (49).…”

Section: T Cellsmentioning

confidence: 99%

“…In another murine model study performed by Wang et al (48), in which subcutaneous vaccination with P. gingivalis ameliorated periodontitis by modulating the Th17/Treg imbalance has been documented (48). They reported that the expression levels of TGFβ-1 and IL-10 mRNA were significantly increased ( p <0.01) implying an adverse role of these cytokines in modulating Th17/Treg imbalance.…”

Section: T Cellsmentioning

confidence: 99%

“…High titers of antibodies to P. gingivalis have been detected in patients with cardiovascular disease and stroke (62). P. gingivalis invades cardiovascular cells and tissues [reviewed by Olsen and Progulske-Fox (63)] and probably contributes to the progression of atherosclerosis (48, 61, 64) as depicted in Fig. 2.…”

Section: Atherosclerosismentioning

confidence: 99%

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Porphyromonas gingivalissuppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

Olsen

Taubman²,

Singhrao

2016

Journal of Oral Microbiology

117

102

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Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer’s disease (AD). Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host’s adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 and increases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, and subsequent IFN-γ secretion by a subset of T cells. The T cells further suppress upregulation of programmed cell death-1 (PD-1)-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response and induces a cytokine pattern in which the Th17 lineage is favored, thereby modulating the Th17/T-regulatory cell (Treg) imbalance. The suppression of IFN-γ-stimulated release of interferon-inducible protein-10 (IP-10) chemokine ligands [ITAC (CXCL11) and Mig (CXCL9)] by P. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion by release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factor beta-1 (TGFβ-1), and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood–brain barrier permeability and inhibit local IFN-γ response by preventing entry of immune cells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infection of the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By the effective manipulation of the armory of adaptive immune suppression through a plethora of virulence factors, P. gingivalis may act as a keystone organism in periodontitis and in related systemic diseases and other remote body inflammatory pathologies.

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Section: T Cellsmentioning

confidence: 85%

Section: T Cellsmentioning

confidence: 99%

Section: T Cellsmentioning

confidence: 99%

Section: Atherosclerosismentioning

confidence: 99%

See 2 more Smart Citations

Porphyromonas gingivalissuppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

Olsen

Taubman²,

Singhrao

2016

Journal of Oral Microbiology

117

102

View full text Add to dashboard Cite

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“…Therefore, NB-UVB light is effective for treatment of various skin diseases that show strong immune responses. NB-UVB might also be useful for treatment of oral mucosal disorders such as periodontitis [8–11], but there has been no report on the use of NB-UVB in dentistry.…”

Section: Introductionmentioning

confidence: 99%

Bactericidal effects of 310 nm ultraviolet light-emitting diode irradiation on oral bacteria

Takada

Matsushita

Horioka³

et al. 2017

BMC Oral Health

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BackgroundUltraviolet (UV) light is used for phototherapy in dermatology, and UVB light (around 310 nm) is effective for treatment of psoriasis and atopic dermatitis. In addition, it is known that UVC light (around 265 nm) has a bactericidal effect, but little is known about the bactericidal effect of UVB light. In this study, we examined the bactericidal effects of UVB-light emitting diode (LED) irradiation on oral bacteria to explore the possibility of using a 310 nm UVB-LED irradiation device for treatment of oral infectious diseases.MethodsWe prepared a UVB (310 nm) LED device for intraoral use to examine bactericidal effects on Streptococcus mutans, Streptococcus sauguinis, Porphyromonas gingivalis, and Fusobacterium nucleatum and also to examine the cytotoxicity to a human oral epithelial cell line (Ca9–22). We also examined the production of nitric oxide and hydrogen peroxide from Ca9–22 cells after irradiation with UVB-LED light.ResultsIrradiation with the 310 nm UVB-LED at 105 mJ/cm2 showed 30–50% bactericidal activity to oral bacteria, though 17.1 mJ/cm2 irradiation with the 265 nm UVC-LED completely killed the bacteria. Ca9–22 cells were strongly injured by irradiation with the 265 nm UVC-LED but were not harmed by irradiation with the 310 nm UVB-LED. Nitric oxide and hydrogen peroxide were produced by Ca9–22 cells with irradiation using the 310 nm UVB-LED. P. gingivalis was killed by applying small amounts of those reactive oxygen species (ROS) in culture, but other bacteria showed low sensitivity to the ROS.ConclusionsNarrowband UVB-LED irradiation exhibited a weak bactericidal effect on oral bacteria but showed low toxicity to gingival epithelial cells. Its irradiation also induces the production of ROS from oral epithelial cells and may enhance bactericidal activity to specific periodontopathic bacteria. It may be useful as a new adjunctive therapy for periodontitis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12903-017-0382-5) contains supplementary material, which is available to authorized users.

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The relationship between T‐helper cell polarization and the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients

Sun

et al. 2019

Clinical & Exp Dental Res

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This study aimed to investigate the relationship between inflammation‐related T‐helper cell polarization and the receptor activator for nuclear factor‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio, which is associated with bone resorption or remodeling of chronic periodontitis patients. Gingival crevicular fluid (GCF) and gingival tissues were obtained from periodontally healthy individuals (PH group) and chronic periodontitis patients (CP group). The GCF levels of IFN‐γ, IL‐4, IL‐17, and IL‐10 linked to T‐helper cell polarization toward the Th1, Th2, Th17, and Treg phenotypes, respectively, were determined by ELISA. The expression levels of these cytokines and the polarized T‐helper cells in gingival tissues were assessed through immunohistochemical and immunofluorescence assays. In addition, the RANKL and OPG expression levels in gingival tissues were detected by immunohistochemical assays, and linear regression analysis was used to identify the potential relationship between T‐helper cell polarization and the RANKL/OPG ratio. In total, 22 individuals and 35 patients were enrolled in the present study. In both GCF and gingival tissues, increased levels of IL‐17 and the decreased levels of IL‐4 and IL‐10 were observed in the CP group. When polarized T‐helper cells were identified in gingival tissues, more Th1 and Th17 cells were found in the CP group, whereas more Th2 and Treg cells were found in the PH group. Although there was no significant difference in OPG expression between the two groups, the RANKL/OPG ratio in the CP group was higher than that in the PH group. The linear regression analysis showed that the presence of more Th1 and Th17 cells correlated with a higher RANKL/OPG ratio, whereas the presence of more Th2 cells correlated with a lower RANKL/OPG ratio. Th1 and Th17 cells are positively correlated and Th2 cells are negatively correlated with the RANKL/OPG ratio. Our data suggest that T‐helper cell polarization is closely linked to the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients.

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Subcutaneous vaccination with Porphyromonas gingivalis ameliorates periodontitis by modulating Th17/Treg imbalance in a murine model

Cited by 42 publications

References 47 publications

Porphyromonas gingivalissuppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

Porphyromonas gingivalissuppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

Bactericidal effects of 310 nm ultraviolet light-emitting diode irradiation on oral bacteria

The relationship between T‐helper cell polarization and the RANKL/OPG ratio in gingival tissues from chronic periodontitis patients

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