scholarly journals Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells

2021 ◽  
Vol 17 (7) ◽  
pp. e1009311
Author(s):  
Sean Ganther ◽  
Allan Radaic ◽  
Erin Malone ◽  
Pachiyappan Kamarajan ◽  
Nai-Yuan Nicholas Chang ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Alveolar Bone ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Oral Microbiome ◽  
Oral Disease ◽  
Periodontal Ligament Cells ◽  
Treponema Denticola ◽  
Host Immune Responses

Periodontal disease is driven by dysbiosis in the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola (T. denticola), is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed significant upregulation of genes associated with extracellular matrix organization and degradation including potentially tissue-specific inducible MMPs that may play novel roles in modulating host immune responses that have yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of expression of either abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs while a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 lead to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data suggest that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.

scholarly journals Nisin Probiotic Prevents Periodontal Disease and Inflammation while Promoting Periodontal Regeneration and a Shift Toward a Healthy Microbiome/Virome

2021 ◽  
Author(s):  
Yvonne Kapila ◽  
Li Gao ◽  
Ryutaro Kuraji ◽  
Martin Jinye Zhang ◽  
April Martinez ◽  
...  
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Lactococcus Lactis ◽  
Pathogenic Bacteria ◽  
Alveolar Bone ◽  
Periodontal Regeneration ◽  
Oral Microbiome ◽  
Oral Disease ◽  
Periodontal Ligament Cells ◽  
Probiotic Treatment

Abstract BackgroundDysbiosis of the oral microbiome mediates chronic periodontal disease, including its characteristic bone loss and host inflammatory response. Realignment of this microbial dysbiosis towards health may prevent disease. Treatment with antibiotics and probiotics can modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. Antibacterial peptides or bacteriocins, such as nisin, and nisin-producing probiotics, Lactococcus lactis, have not been examined in this context, yet warrant further examination because of their biomedical benefits in eradicating biofilms and oral pathogenic bacteria, and modulation of immune mechanisms. The goal of this study was to examine the potential for nisin and a nisin-producing probiotic to abrogate periodontal bone loss and related inflammatory landscape while modulating the composition of the oral microbiome. ResultsA polymicrobial mouse model of periodontal disease was employed for this purpose. In a disease context, nisin and the nisin-producing Lactococcus lactis probiotic significantly decreased the levels of periodontal pathogens, alveolar bone loss, oral inflammatory host response, and host-antibody response to these pathogens. Surprisingly, nisin and/or the nisin-producing L. lactis probiotic also enhanced the number of gingival fibroblasts, periodontal ligament cells, and bone lining cells in response to the polymicrobial infection. Nisin and probiotic treatment significantly shifted the oral bacteriome and virome towards the healthy control state. This shift was characterized by a unique signature; health was associated with a Proteobacteria (Marinobacter sp. B9-2), whereas 3 retroviruses (Golden Hamster Intracisternal A-particle H18, Bat gammaretrovirus, and Porcine type C oncovirus) were associated with disease. Specific disease-associated microbial species were highly correlated with IL-6 levels. ConclusionsNisin’s ability to shift the oral microbiome towards health, mitigate oral disease and the host immune response, and promote a novel regenerative periodontal phenotype, addresses key aspects of the pathogenesis of the disease. These benefits may negate the systemic effects associated with periodontal disease and reveal a new biomedical application for nisin in regenerative medicine.

scholarly journals TheTreponema denticolaChymotrypsin-Like Protease Dentilisin Induces Matrix Metalloproteinase-2-Dependent Fibronectin Fragmentation in Periodontal Ligament Cells

2010 ◽  
Vol 79 (2) ◽  
pp. 806-811 ◽  
Author(s):  
Di Miao ◽  
J. Christopher Fenno ◽  
John C. Timm ◽  
Nam Eok Joo ◽  
Yvonne L. Kapila
Keyword(s):  
Periodontal Disease ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Inflammatory Responses ◽  
Tissue Homeostasis ◽  
Matrix Metalloproteinase 2 ◽  
Periodontal Ligament Cells ◽  
Treponema Denticola ◽  
Periodontal Pathogens ◽  
Culture Supernatants

ABSTRACTPeriodontal disease is a bacterially mediated chronic inflammatory disease that results in destruction of the periodontal ligament (PDL) and alveolar bone that surround and support the dentition. While their precise roles are not well understood, periodontal pathogens, includingTreponema denticola, are believed to initiate the destructive inflammatory responses and dysregulation of tissue homeostasis that characterize the disease. These responses are believed to result from both proinflammatory effects of acylated bacterial membrane components (lipopolysaccharides and lipoproteins) and degradative effects of secreted bacterial proteases. Host-derived matrix metalloproteinases (MMPs) are key enzymes both in tissue homeostasis and tissue destruction. MMP expression is modulated in part by specific proteolytic fragments of fibronectin (FN), which are associated with periodontal disease. FN is a predominant extracellular matrix component in the periodontium. We examined the ability ofTreponema denticolaand its acylated outer membrane PrtP protease complex to induce both activation of MMP-2 and generation of FN fragments in human PDL cell culture supernatants.T. denticolaparent and isogenic mutant strains, as well as MMP-2 small interfering RNA and specific inhibitors of MMP-2 and PrtP activity, were used to examine protein expression, gelatinolytic activity, and FN fragmentation in culture supernatants.T. denticolaand its purified protease induced both MMP-2 activation and FN fragmentation. Here, we demonstrate that PrtP proteolytic activity induces the activation of MMP-2 and that active MMP-2 is required for FN fragmentation. These results suggest a specific mechanism by which theT. denticolaprotease may disrupt homeostatic processes required for the maintenance of periodontal health.

scholarly journals Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells

2021 ◽  
Author(s):  
Sean Ganther ◽  
Allan Radaic ◽  
Nick Chang ◽  
Christian Tafolla ◽  
Ling Zhan ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Periodontal Disease ◽  
Disease Progression ◽  
Inflammatory Cytokines ◽  
Oral Microbiome ◽  
Treponema Denticola ◽  
Periodontal Tissue ◽  
Cellular Processes ◽  
Pro Inflammatory Cytokines

ABSTRACTPeriodontal disease is driven by dysbiosis of the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola, is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed a significant upregulation of genes associated with extracellular matrix organization and degradation, including tissue-specific inducible MMPs that may play novel roles in modulating host immune responses yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of either TLR2 or MyD88 abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs, whereas a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 led to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data support that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.AUTHOR SUMMARYPeriodontal disease is driven by dysbiosis of the oral microbiome, which interacts with host tissues and thereby induces the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs), leading to destruction of the periodontal tissues. Even after clinical intervention, patients with severe periodontal disease are left with a persistent pro-inflammatory transcriptional profile throughout the periodontium. The oral spirochete, Treponema denticola, is consistently found at elevated levels in periodontal lesions and is associated with several pathophysiological effects driving periodontal disease progression. The T. denticola surface-expressed protease complex (dentilisin) has cytopathic effects consistent with periodontal disease pathogenesis. To date, few direct links have been reported between dentilisin and the cellular and tissue processes that drive periodontal tissue destruction at the transcriptional and/or epigenetic levels. Here, we utilize wild type and dentilisin-deficient T. denticola as well as purified dentilisin to characterize dentilisin-dependent activation of intracellular pathways controlling MMP expression and activity. Our results define a role for dentilisin in initiating this signal cascade. Also, our study identified tissue-specific inducible MMPs that may play novel roles in modulating as-yet uncharacterized host responses in periodontal disease. Lastly, T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion. Taken together, our study provides new insights into the molecular mechanisms underpinning periodontal disease progression which could lead to the development of more efficacious therapeutic treatments.

scholarly journals Invasion of Oral and Aortic Tissues by Oral Spirochete Treponema denticola in ApoE−/−Mice Causally Links Periodontal Disease and Atherosclerosis

2014 ◽  
Vol 82 (5) ◽  
pp. 1959-1967 ◽  
Author(s):  
Sasanka S. Chukkapalli ◽  
Mercedes F. Rivera ◽  
Irina M. Velsko ◽  
Ju-Youn Lee ◽  
Hao Chen ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Alveolar Bone ◽  
Tissue Growth ◽  
Aortic Tissue ◽  
Treponema Denticola ◽  
Rapid Progression ◽  
Causative Role ◽  
Igg Antibody ◽  
Content Type ◽  
Periodontal Infection

ABSTRACTTreponema denticolais a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between periodontal disease induced by chronic oralT. denticolainfection and atherosclerosis in hyperlipidemic ApoE−/−mice. ApoE−/−mice (n= 24) were orally infected withT. denticolaATCC 35404 and were euthanized after 12 and 24 weeks.T. denticolagenomic DNA was detected in oral plaque samples, indicating colonization of the oral cavity. Infection elicited significantly (P= 0.0172) higher IgG antibody levels and enhanced intrabony defects than sham infection.T. denticola-infected mice had higher levels of horizontal alveolar bone resorption than sham-infected mice and an associated significant increase in aortic plaque area (P≤ 0.05). Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO) levels and increased serum-oxidized low-density lipoprotein (LDL) levels compared to those of sham-infected mice.T. denticolainfection altered the expression of genes known to be involved in atherosclerotic development, including the leukocyte/endothelial cell adhesion gene (Thbs4), the connective tissue growth factor gene (Ctgf), and the selectin-E gene (Sele). Fluorescentin situhybridization (FISH) revealedT. denticolaclusters in both gingival and aortic tissue of infected mice. This is the first study examining the potential causative role of chronicT. denticolaperiodontal infection and vascular atherosclerosisin vivoin hyperlipidemic ApoE−/−mice.T. denticolais closely associated with periodontal disease and the rapid progression of atheroma in ApoE−/−mice. These studies confirm a causal link for active oralT. denticolainfection with both atheroma and periodontal disease.

scholarly journals Is There a Link between Oropharyngeal Microbiome and Schizophrenia? A Narrative Review

2022 ◽  
Vol 23 (2) ◽  
pp. 846
Author(s):  
Stanislas Martin ◽  
Audrey Foulon ◽  
Wissam El Hage ◽  
Diane Dufour-Rainfray ◽  
Frédéric Denis
Keyword(s):  
Periodontal Disease ◽  
Research Team ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Future Studies ◽  
The Subject ◽  
The Moment ◽  
The Impact ◽  
The Brain

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.

Abstract 180: Increased Atherosclerosis Associated with Periodontal Disease Is Mediated by CD36

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Maria Febbraio ◽  
Paul M Brown
Keyword(s):  
Periodontal Disease ◽  
Alveolar Bone ◽  
Inflammatory Responses ◽  
Disease Risk ◽  
Plasma Cholesterol ◽  
Atherosclerotic Lesion ◽  
Pcr Analysis ◽  
Modified Ldl ◽  
Oxidatively Modified

We previously showed that inflammation, and not hyperlipidemia alone, was necessary for CD36 dependent atherogenesis. Chronic periodontal disease is characterized by a persistent inflammatory state and is epidemiologically associated with cardiovascular disease. We hypothesize that CD36 is an essential link between periodontal disease and atherosclerosis. Low density lipoprotein receptor knock out (LDLR KO) mice and CD36/LDLR double KO mice were infected with the periodontal disease associated bacteria, Porphyromonas gingivalis (Pg), by oral lavage and fed a Western diet for 12 weeks (n = 7-14/group). We assessed periodontal disease, risk factors associated with atherosclerosis, and lesion burden. We conducted studies in isolated macrophages to understand mechanistic differences between the groups. Wild type and CD36 KO macrophages equally phagocytosed bacteria. We measured the cemento-enamel junction of each molar to assess periodontal disease and found that it was significantly increased in infected mice compared with uninfected controls. Histological analysis showed neutrophil, osteoclast and macrophage infiltrates in the alveolar bone of infected mice. Differences in plasma cholesterol, triacylglycerol, insulin resistance and weight gain did not necessarily track with atherosclerosis burden, however blood neutrophils and cytokines were increased in infected LDLR KO mice compared with all other groups. Infected LDLR KO mice had significantly increased atherosclerotic lesion burden compared with uninfected LDLR KO mice, and all of the increased lesion was CD36 dependent. PCR analysis found no evidence for direct infection of atherosclerotic lesions by Pg. In vitro macrophage studies showed that heat killed Pg, lipopolysaccharide (LPS) derived from Pg, oxidatively modified LDL or plasma from infected mice, could not activate the NALP3 inflammasome. Combining heat killed Pg or Pg LPS with oxidatively modified LDL or plasma from infected mice, however, led to significant IL-1 beta secretion that was CD36 and NFkB dependent. Our data suggest that atherosclerosis associated with periodontal disease is mediated by cellular inflammatory responses involving both CD36 and Toll-like receptor.

scholarly journals 2577. Periodontal Disease and the Oral Microbiome in Alcohol-Dependent Individuals

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S895-S896
Author(s):  
Brianna K Meeks ◽  
Jen Barb ◽  
Sarah E Mudra ◽  
Narjis Kazmi ◽  
Ralph T S Tuason, ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Pathogenic Bacteria ◽  
Alveolar Bone ◽  
Severe Disease ◽  
Disease Status ◽  
Oral Microbiome ◽  
Moderate Disease ◽  
Rdna Sequencing ◽  
Severe Periodontitis ◽  
Alcohol Dependent

Abstract Background Periodontal disease results from a polymicrobial infection composed of pathogenic bacteria that colonize the oral cavity, resulting in loss of periodontal attachment and alveolar bone. Periodontitis can increase the risk or exacerbate other comorbidities. Alcohol use increases the risk of periodontitis, but there is little knowledge about periodontitis among people who misuse alcohol. Methods As part of a larger oral and gut microbiome study, this analysis examines the oral microbiome in the occurrence and severity of periodontitis among alcohol-dependent (AD) subjects undergoing a 28-day inpatient alcohol treatment program. Tongue brushings were collected from 22 subjects within the first week of admission, and 16S rDNA sequencing was performed. All subjects had a dental examination during the inpatient stay. This analysis divided periodontal disease status into three major groups–no disease, mild or moderate disease, and severe disease. One-way ANOVA was used to compare microbial genera across the 3 groups. Results Nineteen (86%) of the subjects had periodontitis: 16 had mild or moderate disease, and 3 had severe disease. Statistically different microbial genera in at least one of the three groups (P ≤ 0.05 corresponding to FDR ≤ 0.25) that had a relative abundance of at least 0.5% include: Bifidobacterium, Lactobacillus, Parvimonas, Peptostreptococcus, Porphyromonas, and Treponema. Surprisingly, the subjects with no periodontitis had increased abundances of genera that are often pathogens, Porphyromonas and Peptostreptococcus. Subjects with severe periodontitis had increased abundances of known pathogens Treponema and Parvimonas, as well as Lactobacillus, which has been associated with dental caries. Conclusion We observed that periodontitis accompanies chronic AD, given that 86% of our subjects had the disease. While some microbiome differences for individuals with and without periodontitis were not consistent with the existing literature, this may have many explanations. Future studies should consider how chronic AD could change the microbial ecology of the mouth and lead to further infection as well as utilizing multiple oral sites and a larger sample size to better understand the relationship between AD and periodontal disease. Intramural funds from NIH Disclosures All authors: No reported disclosures.

scholarly journals TheTreponema denticolaPAS Domain-Containing Histidine Kinase Hpk2 Is a Heme Binding Sensor of Oxygen Levels

2018 ◽  
Vol 200 (18) ◽  
Author(s):  
Juni Sarkar ◽  
Daniel P. Miller ◽  
Lee D. Oliver ◽  
Richard T. Marconi
Keyword(s):  
Microbial Community ◽  
Periodontal Disease ◽  
Histidine Kinase ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Treponema Denticola ◽  
Pas Domain ◽  
Adaptive Responses ◽  
Content Type

ABSTRACTPeriodontal disease (PD) results from a shift in the composition of the microbial community of the subgingival crevice. As the bacterial population transitions from Gram-positive bacteria to predominantly Gram-negative anaerobes and spirochetes, dramatic changes occur in the physiological and immunological environment at diseased sites.Treponema denticolathrives in periodontal pockets, indicating that it has a unique ability to adapt to changing environmental conditions. Hpk2 (tde1970), a Per-Arnt-Sim motif (PAS) domain-containing histidine kinase (HK), is part of theT. denticolaHpk2-Rrp2 (tde1969) two-component regulatory (TCR) system. This TCR system is growth phase regulated and has been postulated to play a key role in adaptive responses. In this study, we employ predictive structural analyses and site-directed mutagenesis to investigate the functional role of specific amino acid residues located within the Hpk2 PAS domain. Specific substitutions impacted autophosphorylation (AP), phosphotransfer (PT), oligomerization, and hemin binding. The AP, PT, hemin binding, and oligomerization potential of some mutated Hpk2 proteins differed under aerobic versus anaerobic reaction conditions. The data presented here suggest that the regulatory activity of Hpk2 is linked to diatomic gas levels. In a broader sense, this study highlights the importance of studying proteins produced by anaerobes under conditions that approximate the environment in which they thrive.IMPORTANCEPeriodontal disease affects nearly 60% of the global adult population. Its costs to individuals, and to society as a whole, are enormous. As periodontal disease develops, there is a shift in the composition of the oral microbial community. The bacteria that become dominant are able to cause significant damage to the tissues that support the teeth, leading to tooth loss.Treponema denticolais one of the keystone pathogens associated with periodontal disease. An earlier study demonstrated that the Hpk2 and Rrp2 proteins play an important role in adaptive responses. Here, we explore the role of specific Hpk2 amino acids in environmental sensing and function, using structural analyses and site-directed mutagenesis.

scholarly journals Role of Calprotectin as a Biomarker in Periodontal Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Lili Wei ◽  
Mingwen Liu ◽  
Haofei Xiong
Keyword(s):  
Periodontal Disease ◽  
Calcium Binding ◽  
Alveolar Bone ◽  
Inflammatory Diseases ◽  
Periodontal Tissues ◽  
Adaptive Immune ◽  
S 100 ◽  
And Function ◽  
Plaque Biofilm

Periodontal disease (PD) is a common infectious and inflammatory disease characterised by inflammation of tissues surrounding and supporting the teeth and destruction of the associated alveolar bone, eventually resulting in tooth loss. This disease is caused by periodontopathic bacteria in plaque biofilm and resultant innate and adaptive immune responses in periodontal tissues. Calprotectin (CLP) is a calcium-binding protein of the S-100 protein family and is found to be induced by activated granulocytes, monocytes, and epithelial cells. CLP has been shown to play an important role in numerous inflammatory diseases and disorders. Increasing evidence indicates that CLP is involved in the progression of PD, and its levels may be associated with disease severity and outcome of periodontal treatments. This review will summarise recent studies regarding the presence, regulation, and function of CLP in PD. The findings indicate that CLP may be an effective biomarker for diagnosis and treatment for the PD.

scholarly journals Differential Response of Oral Mucosal and Gingival Cells to Corynebacterium durum, Streptococcus sanguinis, and Porphyromonas gingivalis Multispecies Biofilms

2021 ◽  
Vol 11 ◽  
Author(s):  
Ulrike Redanz ◽  
Sylvio Redanz ◽  
Puthalayai Treerat ◽  
Sivaraman Prakasam ◽  
Li-Jung Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Porphyromonas Gingivalis ◽  
Inflammatory Responses ◽  
Single Species ◽  
Oral Microbiome ◽  
Host Cells ◽  
Oral Disease ◽  
Streptococcus Sanguinis ◽  
Commensal Species ◽  
Multispecies Biofilms

Polymicrobial interactions with oral mucosal surfaces determine the health status of the host. While a homeostatic balance provides protection from oral disease, a dysbiotic polymicrobial community promotes tissue destruction and chronic oral diseases. How polymicrobial communities transition from a homeostatic to a dysbiotic state is an understudied process. Thus, we were interested to investigate this ecological transition by focusing on biofilm communities containing high abundance commensal species and low abundance pathobionts to characterize the host-microbiome interactions occurring during oral health. To this end, a multispecies biofilm model was examined using the commensal species Corynebacterium durum and Streptococcus sanguinis and the pathobiont Porphyromonas gingivalis. We compared how both single and multispecies biofilms interact with different oral mucosal and gingival cell types, including the well-studied oral keratinocyte cell lines OKF4/TERT-1and hTERT TIGKs as well as human primary periodontal ligament cells. While single species biofilms of C. durum, S. sanguinis, and P. gingivalis are all characterized by unique cytokine responses for each species, multispecies biofilms elicited a response resembling S. sanguinis single species biofilms. One notable exception is the influence of P. gingivalis upon TNF-α and Gro-α production in hTERT TIGKs cells, which was not affected by the presence of other species. This study is also the first to examine the host response to C. durum. Interestingly, C. durum yielded no notable inflammatory responses from any of the tested host cells, suggesting it functions as a true commensal species. Conversely, S. sanguinis was able to induce expression and secretion of the proinflammatory cytokines IL-6 and IL-8, demonstrating a much greater inflammatory potential, despite being health associated. Our study also demonstrates the variability of host cell responses between different cell lines, highlighting the importance of developing relevant in vitro models to study oral microbiome-host interactions.

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