Interferon-γ stimulates CD14, TLR2 and TLR4 mRNA expression in gingival fibroblasts increasing responsiveness to bacterial challenge

Lappin, Mark; Brown, Vanessa; Zarić, Svetislav; Lundy, Fionnuala T.; Coulter, Wilson A.; Irwin, Christopher

doi:10.1016/j.archoralbio.2015.10.005

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…coli or P . gingivalis LPS led to increased production of IL‐6 and IL‐8; in addition, the pro‐inflammatory cytokine induced by LPS was abrogated by a blocking antibody to CD14 29 . The previous finding and our results showed that IFN‐γ primes human GFs through the upregulation of innate immune components such as LPS‐recognizing components or molecules involved in antigen presentation, which results in increased responsiveness to bacterial challenge, as determined by pro‐inflammatory molecules.…”

Section: Discussionsupporting

confidence: 70%

“…One study reported the responses of GFs that were infected with oral bacteria following IFN‐γ stimulation, although the study did not apply the concept of polarization GFs. The study showed that IFN‐γ stimulates CD14, TLR2, and TLR4 mRNA expression in GFs increasing responsiveness to bacterial challenge 29 . Pre‐incubation of fibroblasts with IFN‐03A5 and subsequent stimulation with E .…”

Section: Discussionmentioning

confidence: 97%

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IFN‐γ or IL‐4 polarization impacts the response of gingival fibroblasts to oral bacteria

Jang

Choi

2021

J of Periodontal Research

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Background and objective We previously reported that gingival fibroblasts (GFs) can be polarized into functionally distinct subtypes, immune‐activating but tissue‐destructive or tissue‐reparative, in response to T helper (Th1) and Th2 stimuli, respectively. The purpose of this study was to evaluate the effect of polarization on GFs responses to oral bacteria. Methods Unprimed (GF(−)) and IFN‐γ (GF(IFN‐γ)) or IL‐4 primed (GF(IL‐4)) GFs were stimulated with live Fusobacterium nucleatum or Porphyromonas gingivalis. The mRNA expression of IL‐1β, IL‐4, LPS‐recognizing components (Toll‐like receptor (TLR) 4, CD14), molecules involved in antigen presentation (human leukocyte antigen (HLA)‐ABC, HLA‐DP, CD74, CD40), chemokines (C‐X‐C motif chemokine (CXCL)10, CXCL11, chemokine (C‐C motif) ligand 20 (CCL20)), collagen type 1 alpha 1 (COL1A1), and matrix metalloproteinase (MMP)‐1, and the protein levels of IL‐1β, CD14, CXCL11, CCL20, and COL1A1 accumulated in supernatants were analyzed using real‐time PCR and ELISA. Results In response to oral bacteria, the GF(IFN‐γ) significantly upregulated the expression of LPS‐recognizing components, molecules involved in antigen presentation, CXCL10, and CXCL11, whereas the levels of IL‐4 and COL1A1 were downregulated, compared with GF(−). The levels of IL‐1β, CCL20, and MMP‐1 from GF(IFN‐γ) were differently regulated between both bacteria; F. nucleatum was synergistically upregulated, but P. gingivalis was downregulated. The GF(IL‐4) stimulated with both bacteria upregulated the levels of IL‐4, whereas the levels of TLR4 and chemokines were downregulated, compared with GF(−). The regulation of IL‐1β, CD14, CXCL11, CCL20, and COL1A1 proteins showed a similar tendency with mRNA regulation. Conclusion Polarization of GFs with IFN‐γ or IL‐4 affected the way that GFs responded to oral bacteria through up or downregulation of inflammatory responses and extracellular matrix control.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 97%

IFN‐γ or IL‐4 polarization impacts the response of gingival fibroblasts to oral bacteria

Jang

Choi

2021

J of Periodontal Research

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“…Plaque is an important factor in the occurrence and development of periodontal disease, and P. gingivalis has been confirmed to be closely related to periodontitis [ 29 ]. Accordingly, much research has verified that P. gingivalis can infect and invade a variety of host cell types in vitro, including primary human gingival epithelial cells [ 30 ], KB cells [ 31 ], endothelial cells [ 32 ], and gingival fibroblasts [ 33 ]. P. gingivalis has been detected in gingival tissues obtained from patients with periodontitis, indicating an essential effect of invasion in the pathogenesis of periodontitis [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis can invade periodontal ligament stem cells

et al. 2017

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Background Porphyromonas gingivalis is strongly associated with the development, progression, severity and recurrence of periodontitis. Periodontal ligament stem cells (PDLSCs) play an important role in the maintenance of periodontal tissue self-renewal and repair. The purpose of this study was to investigate the ability of P. gingivalis to infect PDLSCs using an in vitro monolayer model.MethodsWe separated and cultured primary PDLSCs using the tissue block with limiting dilution method. The efficiency of P. gingivalis (ATCC 33277) infection of PDLSCs was measured using agar plate culture and quantitative polymerase chain reaction (q-PCR) methods. PDLSCs infected with P. gingivalis were also observed by transmission electron microscopy.ResultsWe assessed stem cell properties including cell morphology, clone formation, growth activity, cell surface antigens and multiple differentiation capacity. The infection rates of P. gingivalis in PDLSC at MOIs of 50, 100, 200, and 500 were 5.83%, 8.12%, 7.77% and 7.53% according to the agar plate culture method. By q-PCR, the efficiencies of P. gingivalis infection of PDLSCs at MOIs of 50, 100, 200, and 500 were 6.74%, 10.56%, 10.36% and 9.78%, respectively. Overall, the infection efficiency based on q-PCR was higher than that according to agar plate culture. Using transmission electron microscopy, we verified that P. gingivalis (ATCC 33277) could infect and invade PDLSCs after 2 h of incubation, and endocytic vacuoles were not found surrounding the internalized bacteria.ConclusionsIn conclusion, our data demonstrate that P. gingivalis can invade PDLSCs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-0950-5) contains supplementary material, which is available to authorized users.

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“…Treatment of MPs with lipopolysaccharide (LPS) and IFN-γ leads to the classical activation of MPs (M1-polarization) which is characterized by the switch from OXPHOS (occuring in resting MPs) to induced glucose uptake, aerobic glycolysis with lactate production, enhanced PPP and decreased TCA activities (Kelly and O'Neill, 2015). However, this switch is also induced by LPS alone (Krawczyk et al, 2010; O'Neill, 2014), indicating that IFN-γ plays in this context mainly a co-stimulatory role, probably by enhancing the expression of the LPS receptors CD14 and TLR4 (Lappin et al, 2016).…”

Section: Modulation Of the Cell Metabolism By Interferons (Ifn) Leadimentioning

confidence: 99%

How Viral and Intracellular Bacterial Pathogens Reprogram the Metabolism of Host Cells to Allow Their Intracellular Replication

Eisenreich

Rudel

Heesemann

et al. 2019

Front. Cell. Infect. Microbiol.

160

145

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Viruses and intracellular bacterial pathogens (IBPs) have in common the need of suitable host cells for efficient replication and proliferation during infection. In human infections, the cell types which both groups of pathogens are using as hosts are indeed quite similar and include phagocytic immune cells, especially monocytes/macrophages (MOs/MPs) and dendritic cells (DCs), as well as nonprofessional phagocytes, like epithelial cells, fibroblasts and endothelial cells. These terminally differentiated cells are normally in a metabolically quiescent state when they are encountered by these pathogens during infection. This metabolic state of the host cells does not meet the extensive need for nutrients required for efficient intracellular replication of viruses and especially IBPs which, in contrast to the viral pathogens, have to perform their own specific intracellular metabolism to survive and efficiently replicate in their host cell niches. For this goal, viruses and IBPs have to reprogram the host cell metabolism in a pathogen-specific manner to increase the supply of nutrients, energy, and metabolites which have to be provided to the pathogen to allow its replication. In viral infections, this appears to be often achieved by the interaction of specific viral factors with central metabolic regulators, including oncogenes and tumor suppressors, or by the introduction of virus-specific oncogenes. Less is so far known on the mechanisms leading to metabolic reprogramming of the host cell by IBPs. However, the still scant data suggest that similar mechanisms may also determine the reprogramming of the host cell metabolism in IBP infections. In this review, we summarize and compare the present knowledge on this important, yet still poorly understood aspect of pathogenesis of human viral and especially IBP infections.

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Interferon-γ stimulates CD14, TLR2 and TLR4 mRNA expression in gingival fibroblasts increasing responsiveness to bacterial challenge

Cited by 11 publications

References 27 publications

IFN‐γ or IL‐4 polarization impacts the response of gingival fibroblasts to oral bacteria

IFN‐γ or IL‐4 polarization impacts the response of gingival fibroblasts to oral bacteria

Porphyromonas gingivalis can invade periodontal ligament stem cells

How Viral and Intracellular Bacterial Pathogens Reprogram the Metabolism of Host Cells to Allow Their Intracellular Replication

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