Microbiome-mediated incapacitation of interferon lambda production in the oral mucosa

2021 ◽  
Vol 118 (51) ◽  
pp. e2105170118
Author(s):  
Carlos J. Rodriguez-Hernandez ◽  
Kevin J. Sokoloski ◽  
Kendall S. Stocke ◽  
Himabindu Dukka ◽  
Shunying Jin ◽  
...  

Here, we show that Porphyromonas gingivalis (Pg), an endogenous oral pathogen, dampens all aspects of interferon (IFN) signaling in a manner that is strikingly similar to IFN suppression employed by multiple viral pathogens. Pg suppressed IFN production by down-regulating several IFN regulatory factors (IRFs 1, 3, 7, and 9), proteolytically degrading STAT1 and suppressing the nuclear translocation of the ISGF3 complex, resulting in profound and systemic repression of multiple interferon-stimulated genes. Pg-induced IFN paralysis was not limited to murine models but was also observed in the oral tissues of human periodontal disease patients, where overabundance of Pg correlated with suppressed IFN generation. Mechanistically, multiple virulence factors and secreted proteases produced by Pg transcriptionally suppressed IFN promoters and also cleaved IFN receptors, making cells refractory to exogenous IFN and inducing a state of broad IFN paralysis. Thus, our data show a bacterial pathogen with equivalence to viruses in the down-regulation of host IFN signaling.

Ensho ◽  
1998 ◽  
Vol 18 (4) ◽  
pp. 259-264
Author(s):  
Kenji Yamamoto ◽  
Tomoko Kadowaki ◽  
Kuniaki Okamoto ◽  
Naoko Abe ◽  
Koji Nakayama

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 240.2-241
Author(s):  
F. Zekre ◽  
R. Cimaz ◽  
M. Paul ◽  
J. L. Stephan ◽  
S. Paul ◽  
...  

Background:Idiopathic juvenile arthritis (JIA) is a heterogeneous group of pathologies whose origin remains unknown at present (1). They are characterised by a systemic inflammatory and joint disease affecting children under 16 years of age. The current classification groups the different forms of JIA into 7 distinct entities (systemic forms, polyarticular forms with or without rheumatoid factors, oligoarticular forms, inflammatory arthritis associated with enthesopathies (ERA), arthritis associated with psoriasis and unclassifiable arthritis). Exact etiology of JIA is still unknown. To date, the various hypotheses put forward on the occurrence of JIAs integrate the genetic and environmental framework.The link between periodontal disease and rheumatoid arthritis (RA) is largely reported. Recently, Porphyromonas gingivalis (P. gingivalis) infection explained the occurrence of arthritis in rodent and in RA (2). Several studies mention the beneficial effect of P. gingivalis treatment on disease activity.Currently, there are very few studies on the prevalence of P. gingivalis in patients with JIA and the possible involvement of the germ in the development of inflammatory joint diseases in the pediatric population(3)(4).Objectives:The objective of our study is to determine presence of high IgG antibodies against P. gingivalis and Prevotella Intermedia in a cohort of patients with JIA compared to a control population and to determine variation of level according to sub-classes of JIA.Methods:Sera were obtained from 101 patients satisfying the ILAR classification criteria for JIA and in 25 patients with two other dysimmune disorders (type 1 diabetes and juvenile inflammatory bowel disease). Level of IgG antibodies against P. gingivalis and Prevotella Intermedia were obtained by homemade ELISA already used previously (5).Results:In the JIA group, major children were oligarthritis (47.5%), polyarthritis represents 31.7% of JIAs, ERA and systemic forms of JIA are respectively 9 and 11%. For the control group, 10 (40%) children had diabetes and 15 (60%) had IBD.Levels of anti-P. gingivalis anti-Prevotella Intermedia antibodies were higher in AJI group compared at control groups (P<0.01, P<0.05). Theses difference are mainly related to oligoarthritis and ERA subsets for both P. gingivalis and Prevotella Intermedia.Figure 1.Relative titer of antibodies to P. gingivalis and anti Prevotella intermedia. *: P<0.05; **: P<0.01; ***: P<0.001. P. gingivalis (control vs oligoarthritis p= 0.0032. control vs ERA p= 0.0092). Prevotella intermedia (control vs oligoarthritis p= 0.0194. control vs ERA p= 0.0039).Conclusion:We confirmed high level of anti-P. gingivalis and anti-Prevotella intermedia antibodies in JIA compared to other inflammatory disorders. For the first time, we observed that this high level was mainly in oligoarthritis and ERA. Further investigations are required to investigate involvement of oral dysbiosis in AJI pathogenesis. As observed in RA, it could be a new way to integrate in JIA therapy management.References:[1]Thatayatikom A, De Leucio A. Juvenile Idiopathic Arthritis (JIA). StatPearls Publishing; 2020[2]Cheng Z, Meade J, Mankia K, Emery P, Devine DA. Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):19–30.[3]Romero-Sánchez C, Malagón C, Vargas C, Fernanda Torres M, Moreno LC, Rodríguez C, et al. Porphyromonas Gingivalis and IgG1 and IgG2 Subclass Antibodies in Patients with Juvenile Idiopathic Arthritis. J Dent Child Chic Ill. 2017 May 15;84(2):72–9.[4]Lange L, Thiele GM, McCracken C, Wang G, Ponder LA, Angeles-Han ST, et al. Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016 Feb 9[5]Rinaudo-Gaujous M, Blasco-Baque V, Miossec P, Gaudin P, Farge P, Roblin X, et al. Infliximab Induced a Dissociated Response of Severe Periodontal Biomarkers in Rheumatoid Arthritis Patients. J Clin Med. 2019 May 26;8(5).Disclosure of Interests:None declared.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hong Li ◽  
Xiang Ma ◽  
Yanqiong Tang ◽  
Dan Wang ◽  
Ziding Zhang ◽  
...  

Abstract Background Aeromonas veronii is a bacterial pathogen in aquaculture, which produces virulence factors to enable it colonize and evade host immune defense. Given that experimental verification of virulence factors is time-consuming and laborious, few virulence factors have been characterized. Moreover, most studies have only focused on single virulence factors, resulting in biased interpretation of the pathogenesis of A. veronii. Results In this study, a PPI network at genome-wide scale for A. veronii was first constructed followed by prediction and mapping of virulence factors on the network. When topological characteristics were analyzed, the virulence factors had higher degree and betweenness centrality than other proteins in the network. In particular, the virulence factors tended to interact with each other and were enriched in two network modules. One of the modules mainly consisted of histidine kinases, response regulators, diguanylate cyclases and phosphodiesterases, which play important roles in two-component regulatory systems and the synthesis and degradation of cyclic-diGMP. Construction of the interspecies PPI network between A. veronii and its host Oreochromis niloticus revealed that the virulence factors interacted with homologous proteins in the host. Finally, the structures and interacting sites of the virulence factors during interaction with host proteins were predicted. Conclusions The findings here indicate that the virulence factors probably regulate the virulence of A. veronii by involving in signal transduction pathway and manipulate host biological processes by mimicking and binding competitively to host proteins. Our results give more insight into the pathogenesis of A. veronii and provides important information for designing targeted antibacterial drugs.


2011 ◽  
Vol 193 (16) ◽  
pp. 4259-4260 ◽  
Author(s):  
T. Watanabe ◽  
F. Maruyama ◽  
T. Nozawa ◽  
A. Aoki ◽  
S. Okano ◽  
...  

1991 ◽  
Vol 59 (12) ◽  
pp. 4363-4370 ◽  
Author(s):  
A M De Nardin ◽  
H T Sojar ◽  
S G Grossi ◽  
L A Christersson ◽  
R J Genco

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 1499
Author(s):  
Endang Winiati Bachtiar ◽  
Citra F. Putri ◽  
Retno D. Soejoedono ◽  
Boy M. Bachtiar

Porphyromonas gingivalis has virulence factors such as gingipain and lipopolysaccharide, causing bacteremia to reach the brain and activate neuroinflammatory release cytokines. This study analyzed the effect of the co-culture of neuron cells with P. gingivalis coated with anti-P. gingivalis antibodies against cytokines produced by neuron cells. The gene expressions of the TNF, IL1B, iNOS2 in neurons was evaluated using RT-qPCR. The results showed that P. gingivalis coated with anti-P. gingivalis antibody before co-culture with neuron cells could decrease the gene expression of TNF, IL1B, and iNOS2 of neuron cells.


2021 ◽  
Vol 6 (1) ◽  
pp. 72
Author(s):  
Lailatul Qomariyah ◽  
Fransiska Uli Arta Panjaitan

ABSTRACTBackground: Chronic periodontitis is a periodontal disease with 80% of all cases of periodontitis. The major causes are the accumulation of plaque and bacteria. The dominant bacteria in chronic periodontitis is Porphyromonas gingivalis. Treatment of chronic periodontitis can be done by scaling and root planing and supporting therapy by using mouthwash such as Chlorhexidine gluconate 0.2% which is the gold standard in the treatment of periodontal disease. Chlorhexidine gluconate 0.2% has disadvantages so that nowadays research on herbal plants is being done to find alternative medicines that are more effective. Ramania (Bouea machropylla Griffith) leaf contains flavonoids that have antibacterial properties. Objective: To analyze the antibacterial effectivity of the flavonoid fraction of Ramania leaf extract against Porphyromonas gingivalis that causes chronic periodontitis. Method: True experimental study and post-test with control group design consisting of 5 treatment groups, namely flavonoid fraction of ramania leaf extract with concentrations of 0.1%, 0.3%, and 0.5%, chlorhexidine gluconate 0.2% as a control positive and aquadest as a negative control. Each group was repeated 6 times. Antibacterial tests using the dilution method with inhibitory rates calculated using a UV-Vis spectrophotometer and killing rates were calculated using a Colony Counter. Results: The average difference in absorbance values obtained inhibitory rates at concentrations of 0.1%, 0.3%, and 0.5%. One Way Anova Test showed a significance value of 0,000 (p < 0.05). The average number of colonies after 24 hours incubation showed the results of a kill rates in the concentration group of 0.3%, 0.5%, and positive control. The Kruskal Wallis test showed a significance value of 0,000 (p < 0.05). Conclusion: The minimum inhibitory concentration (MIC) was obtained at a concentration of 0.1% and the minimum bactericidal concentration (MBC) was obtained at 0.3% concentration.Keywords: Flavonoid Fraction, MBC, MIC, Porphyromonas Gingivalis, Ramania Leaf Extract.


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