Porphyromonas gingivalis bypasses epithelial barrier and modulates fibroblastic inflammatory response in an in vitro 3D spheroid model

Bugueno, Isaac Maximiliano; Batool, Fareeha; Keller, Laetitia; Kuchler‐Bopp, Sabine; Benkirane‐Jessel, Nadia; Huck, Olivier

doi:10.1038/s41598-018-33267-4

Cited by 33 publications

(29 citation statements)

References 61 publications

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“…Previous studies have reported that P. gingivalis , present in our “periodontitis-associated” biofilm model, is able to be internalised by and survive within gingival epithelial cells 39–41 . Likewise, ensuing research has found that this organism is capable of bypassing the epithelial barrier in a 3D gingival epithelial and fibroblast spheroid model to induce an inflammatory response 42 . Thus, future work would benefit from assessing whether these contact-dependent mechanisms can be mimicked in this model.…”

Section: Discussionmentioning

confidence: 99%

Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells

Brown

Johnston

Delaney

et al. 2019

Sci Rep

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The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with “health”, “gingivitis” and “periodontitis”. These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14+ monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by “gingivitis-associated” biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface.

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Section: Discussionmentioning

confidence: 99%

Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells

Brown

Johnston

Delaney

et al. 2019

Sci Rep

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“…Culture models made with other cell types have yielded similar results. Significant differences in the inflammatory response of cells infected with P. gingivalis (W50 and 33277 strains) were observed between 3D cultures made with collagen‐embedded fibroblasts overlaid with layers of oral ECs and 2D monolayers of oral epithelial cells (Bugueno et al, ; Pinnock, Murdoch, Moharamzadeh, Whawell, & Douglas, ). The increased secretion of proinflammatory cytokines in 3D and 2D cells treated with Aa‐LPS at the cytokine concentration associated with inflammation suggests a potential role of this antigen in the endothelial dysfunction associated with periodontopathogens (Liljestrand et al, ).…”

Section: Discussionmentioning

confidence: 99%

Differential responses of endothelial cells on three‐dimensional scaffolds to lipopolysaccharides from periodontopathogens

Gualtero

Lafaurie

Fontanilla

2019

Molecular Oral Microbiology

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Studies have been conducted on the pathogenicity of periodontopathogens in cultures of endothelial cells on two‐dimensional (2D) polystyrene surfaces, where the monolayer formed is not exposed to proteins of the subendothelial matrix. In this work, we developed a culture system by seeding human coronary artery endothelial cells (HCAECs) onto three‐dimensional (3D) scaffolds of collagen type I, a subendothelial protein. The inflammatory responses of the HCAEC monolayers, formed either on 3D scaffolds or directly on a 2D polystyrene plate, to lipopolysaccharide (LPS) from Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) were evaluated. The transcription of 3 genes, the secretion of 40 cytokines and 2 prostanoids, and the adhesion of monocytes to 2D and 3D cultures with or without exposure to lipopolysaccharides (control) were assessed. HCAECs exhibited differences in transcriptional and secretory profiles between the 3D and 2D models. In addition, the inflammatory responses of HCAEC to Aa‐LPS and Pg‐LPS differed between the two models. In 3D cultures treated with Aa‐LPS, the levels of IL‐8, RANTES, G‐CSF, ICAM‐1, IL‐6, and TXA2 were significantly higher than those in the controls. In 2D cultures treated with Aa‐LPS, IL‐8, RANTES, G‐CSF, ICAM‐1, TNF‐RI, PGI2, and TXA2 levels were significantly higher than those in their controls. In the presence of Aa‐LPS, monocyte adhesion did not differ between treated and control 3D cultures but was significantly higher in treated 2D cultures than in the controls. In response to Pg‐LPS, cytokine‐prostaglandin secretion and monocyte adhesion did not differ between 3D and 2D cultures. These data indicate that HCAECs respond differently to these two types of LPS.

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“…Bacterial culture. The P. gingivalis strain (ATCC 33277) was purchased from the ATCC and cultured as described previously 13 . Briefly, bacterial culture was performed under strict anaerobic conditions at 37 °C in brain-heart infusion medium (BHI) (Sigma) supplemented with hemin (5 μg/mL) and menadione (1 μg/mL).…”

Section: Methodsmentioning

confidence: 99%

A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction

Batool

Stutz

Petit

et al. 2020

Sci Rep

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The control of inflammation and infection is crucial for periodontal wound healing and regeneration. M101, an oxygen carrier derived from Arenicola marina, was tested for its anti-inflammatory and anti-infectious potential based on its anti-oxidative and tissue oxygenation properties. In vitro, no cytotoxicity was observed in oral epithelial cells (EC) treated with M101. M101 (1 g/L) reduced significantly the gene expression of pro-inflammatory markers such as TNF-α, NF-κΒ and RANKL in P. gingivalis-LPS stimulated and P. gingivalis-infected EC. The proteome array revealed significant down-regulation of pro-inflammatory cytokines (IL-1β and IL-8) and chemokine ligands (RANTES and IP-10), and upregulation of pro-healing mediators (PDGF-BB, TGF-β1, IL-10, IL-2, IL-4, IL-11 and IL-15) and, extracellular and immune modulators (TIMP-2, M-CSF and ICAM-1). M101 significantly increased the gene expression of Resolvin-E1 receptor. Furthermore, M101 treatment reduced P. gingivalis biofilm growth over glass surface, observed with live/dead analysis and by decreased P. gingivalis 16 s rRNA expression (51.7%) (p < 0.05). In mice, M101 reduced the clinical abscess size (50.2%) in P. gingivalis-induced calvarial lesion concomitant with a decreased inflammatory score evaluated through histomorphometric analysis, thus, improving soft tissue and bone healing response. Therefore, M101 may be a novel therapeutic agent that could be beneficial in the management of P. gingivalis associated diseases.

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Porphyromonas gingivalis bypasses epithelial barrier and modulates fibroblastic inflammatory response in an in vitro 3D spheroid model

Cited by 33 publications

References 61 publications

Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells

Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells

Differential responses of endothelial cells on three‐dimensional scaffolds to lipopolysaccharides from periodontopathogens

A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction

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