Oral infection with Porphyromonas gingivalis and systemic cytokine profile in C57BL/6.KOR‐ApoEshl mice

Miyauchi, Sayuri; Maekawa, Tomoki; Aoki, Y.; Miyazawa, Haruna; Tabeta, Koichi; Nakajima, Takako Eguchi; Yamazaki, Kazuhisa

doi:10.1111/j.1600-0765.2011.01441.x

Cited by 27 publications

(26 citation statements)

References 43 publications

(41 reference statements)

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“…Like periodontitis, atherosclerosis is a complex condition with a suspected microbial etiology in which P. gingivalis is attracting increasing attention for its possible role in accelerating disease progression (59, 60). Unsurprisingly, therefore, pathogenesis of atherosclerosis is associated with both innate and adaptive immune responses.…”

Section: Atherosclerosismentioning

confidence: 99%

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

Olsen

Taubman²,

Singhrao

2016

Journal of Oral Microbiology

112

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: Atherosclerosismentioning

confidence: 99%

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

Olsen

Taubman²,

Singhrao

2016

Journal of Oral Microbiology

112

102

View full text Add to dashboard Cite

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“…The role of Th17 cells in periodontitis is still under investigation, with various lines of evidence suggesting that it can either drive or protect against disease development [8,9]. While the effect of P. gingivalis and the role of cytokines in inflammation of the oral tissues have been explored, only a few preclinical studies have evaluated the systemic effect of periodontitis [10,11] and how it may affect the development of other diseases in preclinical models. The bidirectional association of periodontitis with other diseases, including cardiovascular disease [12], diabetes mellitus [13], and rheumatoid arthritis (RA) [14], underscores the relevance of understanding the cytokine networks implicated in such associations.…”

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

et al. 2013

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IntroductionClinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model.MethodsDBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression.ResultsMice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group.ConclusionsChronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.

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“…Accumulating evidence indicated a close relationship between periodontal infection and AS [6]–[8]. P.gingivalis , as the main pathogen of chronic periodontal disease, is a gram-negative anaerobic bacterium in the subgingival dental plaque.…”

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis Infection Reduces Regulatory T Cells in Infected Atherosclerosis Patients

Yang

Liu

et al. 2014

PLoS ONE

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Increasing evidence has shown periodontal pathogen Porphyromonas gingivalis (P.gingivalis) infection contributes to atherosclerosis (AS) progression. P.gingivalis fimbriae act as an important virulence factor in AS. Regulatory T cells (Tregs) may play a crucial role in autoimmune response during this process. However, whether P.gingivalis infection is associated with Tregs dysregulation during AS is still unknown and the prevalence of different P.gingivalis FimA genotypes during this process is unclear. Here we analyzed the distribution of Tregs and in P.gingivalis-infected atherosclerotic patients to reveal the relationship between P.gingivalis infection and Tregs reduction/dysfunction and to elucidate their role in periodontitis-AS interaction. FimA genotype was also examined to determine the prevalence of fimbriae. Our results showed that P.gingivalis infection reduced Tregs in atherosclerotic patients compared with non-atherosclerotic patients and health controls. Concentration of TGF-β1, which plays an important role in the development of Tregs, also decreased in P.gingivalis infected patients. Furthermore, type II FimA seems to show higher prevalence than the other five detected types. The population of Tregs further decreased in patients with type II FimA compared with the other types. P.gingivlias FimA genotype II was the dominant type associated with decreased Treg population. These results indicate that P.gingivalis infection may be associated with Tregs dysregulation in AS; type II FimA may be a predominant genotype in this process.

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Oral infection with Porphyromonas gingivalis and systemic cytokine profile in C57BL/6.KOR‐ApoE^shl mice

Abstract: These data demonstrate that oral infection with P. gingivalis induces alterations in systemic cytokine production. These cytokines could play roles in the development not only of periodontitis but also of atherosclerosis.

Cited by 27 publications

References 43 publications

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

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

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

Porphyromonas gingivalis Infection Reduces Regulatory T Cells in Infected Atherosclerosis Patients

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