The Capsule of Porphyromonas gingivalis Leads to a Reduction in the Host Inflammatory Response, Evasion of Phagocytosis, and Increase in Virulence
01 Nov 2011-Infection and Immunity (American Society for Microbiology)-Vol. 79, Iss: 11, pp 4533-4542
TL;DR: The results indicate that the P. gingivalis capsule plays an important role in aiding evasion of host immune system activation, promoting survival of the bacterium within host cells, and increasing virulence.
Abstract: Periodontal disease is a chronic oral inflammatory disease that is triggered by bacteria such as Porphyromonas gingivalis. P. gingivalis strains exhibit great heterogeneity, with some strains being encapsulated while others are nonencapsulated. Although the encapsulated strains have been shown to be more virulent in a mouse abscess model, so far the role of the capsule in P. gingivalis interactions with host cells is not well understood and its role in virulence has not been defined. Here, we investigated the contribution of the capsule to triggering a host response following microbial infection, as well as its protective role following bacterial internalization by host phagocytic cells with subsequent killing, using the encapsulated P. gingivalis strain W50 and its isogenic nonencapsulated mutant, PgC. Our study shows significant time-dependent upregulation of the expression of various groups of genes in macrophages challenged with both the encapsulated and nonencapsulated P. gingivalis strains. However, cells infected with the nonencapsulated strain showed significantly higher upregulation of 9 and 29 genes at 1 h and 8 h postinfection, respectively, than cells infected with the encapsulated strain. Among the genes highly upregulated by the nonencapsulated PgC strain were ones coding for cytokines and chemokines. Maturation markers were induced at a 2-fold higher rate in dendritic cells challenged with the nonencapsulated strain for 4 h than in dendritic cells challenged with the encapsulated strain. The rates of phagocytosis of the nonencapsulated P. gingivalis strain by both macrophages and dendritic cells were 4.5-fold and 7-fold higher, respectively, than the rates of phagocytosis of the encapsulated strain. On the contrary, the survival of the nonencapsulated P. gingivalis strain was drastically reduced compared to the survival of the encapsulated strain. Finally, the encapsulated strain exhibited greater virulence in a mouse abscess model. Our results indicate that the P. gingivalis capsule plays an important role in aiding evasion of host immune system activation, promoting survival of the bacterium within host cells, and increasing virulence. As such, it is a major virulence determinant of P. gingivalis. © 2011, American Society for Microbiology.
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TL;DR: An overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity is provided.
Abstract: Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that causes destruction to periodontal tissue either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity.
484 citations
Cites background from "The Capsule of Porphyromonas gingiv..."
...According to Singh et al. (2011), increased encapsulation is also correlated with increased resistance to phagocytosis, serum resistance, and decreased induction of polymorphonuclear leukocyte chemiluminescence....
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...On top of its immunomodulating properties, capsule was shown to promote virulence using mouse abscess model by reducing phagocytosis and thereby increasing bacterial survival within host cells, and ultimately a long-term inflammatory response (Singh et al., 2011)....
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Brown University1, Harvard University2, Imperial College London3, German Cancer Research Center4, Aarhus University5, International Agency for Research on Cancer6, South University7, Institut Gustave Roussy8, National and Kapodistrian University of Athens9, Academy of Athens10, University of Naples Federico II11, Utrecht University12, University of Tromsø13, Andalusian School of Public Health14, Umeå University15, Karolinska Institutet16, University of Gothenburg17, Lund University18, University of Cambridge19, Medical Research Council20, University of Oxford21
TL;DR: Monitoring of antibodies to oral bacteria in prediagnosis blood samples found that increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer.
Abstract: Objective Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study.
Design We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index.
Results Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83).
Conclusions Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.
291 citations
TL;DR: The links between the gut microbiota, gut barrier function and the onset of low-grade inflammation in the development of gastrointestinal cancer are reviewed and the mechanisms by which specific microorganism-associated molecular patterns crosstalk with the immune system are described.
Abstract: Overweight and obesity are associated with increased risk of developing metabolic disorders such as diabetes and cardiovascular diseases. However, besides these metabolic diseases, excess body weight is also associated with different cancers, including gastrointestinal cancers, such as liver, pancreatic and colon cancers. Inflammation is a common feature of both obesity and cancer; however, the origin of this inflammation has been largely debated. Over the past decade, growing evidence has shown that the composition of the gut microbiota and its activity might be associated not only with the onset of inflammation but also with metabolic disorders and cancer. Here, we review the links between the gut microbiota, gut barrier function and the onset of low-grade inflammation in the development of gastrointestinal cancer. We also describe the mechanisms by which specific microorganism-associated molecular patterns crosstalk with the immune system and how the metabolic activity of bacteria induces specific signalling pathways beyond the gut that eventually trigger carcinogenesis.
237 citations
TL;DR: Results indicate that microbial communities respond to long‐term warming by enriching carbon degradation, nutrient cycling (nitrogen and phosphorous) and stress response gene families, and is the most comprehensive functional gene array for microbial community analysis.
Abstract: Micro-organisms play critical roles in many important biogeochemical processes in the Earth's biosphere. However, understanding and characterizing the functional capacity of microbial communities are still difficult due to the extremely diverse and often uncultivable nature of most micro-organisms. In this study, we developed a new functional gene array, GeoChip 4, for analysing the functional diversity, composition, structure, metabolic potential/activity and dynamics of microbial communities. GeoChip 4 contained approximately 82 000 probes covering 141 995 coding sequences from 410 functional gene families related to microbial carbon (C), nitrogen (N), sulphur (S), and phosphorus (P) cycling, energy metabolism, antibiotic resistance, metal resistance/reduction, organic remediation, stress responses, bacteriophage and virulence. A total of 173 archaeal, 4138 bacterial, 404 eukaryotic and 252 viral strains were targeted, providing the ability to analyse targeted functional gene families of micro-organisms included in all four domains. Experimental assessment using different amounts of DNA suggested that as little as 500 ng environmental DNA was required for good hybridization, and the signal intensities detected were well correlated with the DNA amount used. GeoChip 4 was then applied to study the effect of long-term warming on soil microbial communities at a Central Oklahoma site, with results indicating that microbial communities respond to long-term warming by enriching carbon degradation, nutrient cycling (nitrogen and phosphorous) and stress response gene families. To the best of our knowledge, GeoChip 4 is the most comprehensive functional gene array for microbial community analysis.
184 citations
Cites background from "The Capsule of Porphyromonas gingiv..."
...The bacterial capsule promotes virulence by reducing host immune responses (Singh et al. 2011)....
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TL;DR: The objective is to identify macrophage-mediated events central to the inflammatory basis of chronic diseases, with an emphasis on how control of macrophages function can be used to prevent or treat harmful outcomes linked to uncontrolled inflammation.
Abstract: Inflammation is a complex reaction to injurious agents and includes vascular responses, migration, and activation of leukocytes. Inflammation starts with an acute reaction, which evolves into a chronic phase if allowed to persist unresolved. Acute inflammation is a rapid process characterized by fluid exudation and emigration of leukocytes, primarily neutrophils, whereas chronic inflammation extends over a longer time and is associated with lymphocyte and macrophage infiltration, blood vessel proliferation, and fibrosis. Inflammation is terminated when the invader is eliminated, and the secreted mediators are removed; however, many factors modify the course and morphologic appearance as well as the termination pattern and duration of inflammation. Chronic inflammatory illnesses such as diabetes, arthritis, and heart disease are now seen as problems that might have an impact on the periodontium. Reciprocal effects of periodontal diseases are potential factors modifying severity in the progression of systemic inflammatory diseases. Macrophages are key cells for the inflammatory processes as regulators directing inflammation to chronic pathological changes or resolution with no damage or scar tissue formation. As such, macrophages are involved in a remarkably diverse array of homeostatic processes of vital importance to the host. In addition to their critical role in immunity, macrophages are also widely recognized as ubiquitous mediators of cellular turnover and maintenance of extracellular matrix homeostasis. In this review, our objective is to identify macrophage-mediated events central to the inflammatory basis of chronic diseases, with an emphasis on how control of macrophage function can be used to prevent or treat harmful outcomes linked to uncontrolled inflammation.
152 citations
Cites background from "The Capsule of Porphyromonas gingiv..."
...Nevertheless, this is the prevailing paradigm, since the tools for analyses of the events at multiple levels are just being incorporated into oral research (Singh et al., 2011; Hasturk et al., 2012)....
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...…results of studies that use high-throughput measurements to generate a systems-biology approach, the complex nature of host–bacteria interactions in a highly complex environment of the oral cavity is being redefined (Bakthavatchalu et al., 2011; Mishima and Sharma, 2011; Singh et al., 2011)....
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References
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TL;DR: The purpose of the present investigation was to attempt to define communities using data from large numbers of plaque samples and different clustering and ordination techniques, which related strikingly to clinical measures of periodontal disease particularly pocket depth and bleeding on probing.
Abstract: It has been recognized for some time that bacterial species exist in complexes in subgingival plaque. The purpose of the present investigation was to attempt to define such communities using data from large numbers of plaque samples and different clustering and ordination techniques. Subgingival plaque samples were taken from the mesial aspect of each tooth in 185 subjects (mean age 51 +/- 16 years) with (n = 160) or without (n = 25) periodontitis. The presence and levels of 40 subgingival taxa were determined in 13,261 plaque samples using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments were made at 6 sites per tooth at each visit. Similarities between pairs of species were computed using phi coefficients and species clustered using an averaged unweighted linkage sort. Community ordination was performed using principal components analysis and correspondence analysis. 5 major complexes were consistently observed using any of the analytical methods. One complex consisted of the tightly related group: Bacteroides forsythus, Porphyromonas gingivalis and Treponema denticola. The 2nd complex consisted of a tightly related core group including members of the Fusobacterium nucleatum/periodonticum subspecies, Prevotella intermedia, Prevotella nigrescens and Peptostreptococcus micros. Species associated with this group included: Eubacterium nodatum, Campylobacter rectus, Campylobacter showae, Streptococcus constellatus and Campylobacter gracilis. The 3rd complex consisted of Streptococcus sanguis, S. oralis, S. mitis, S. gordonii and S. intermedius. The 4th complex was comprised of 3 Capnocytophaga species, Campylobacter concisus, Eikenella corrodens and Actinobacillus actinomycetemcomitans serotype a. The 5th complex consisted of Veillonella parvula and Actinomyces odontolyticus. A. actinomycetemcomitans serotype b, Selenomonas noxia and Actinomyces naeslundii genospecies 2 (A. viscosus) were outliers with little relation to each other and the 5 major complexes. The 1st complex related strikingly to clinical measures of periodontal disease particularly pocket depth and bleeding on probing.
4,143 citations
"The Capsule of Porphyromonas gingiv..." refers background in this paper
...gingivalis, an anaerobic Gram-negative member of the Cytophaga-Bacteroidetes family, belongs to a “red complex” of species associated with chronic periodontal infections (25, 43, 50)....
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"The Capsule of Porphyromonas gingiv..." refers background in this paper
...Although bacterial pathogens are required to initiate periodontal disease, their presence alone is not sufficient to cause the severe tissue destruction seen clinically (7, 8, 23)....
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TL;DR: The current understanding of myeloid lineage development is reviewed and the developmental pathways and cues that drive differentiation are described, which are central to the development of immunologic memory and tolerance in mice.
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...Furthermore, dendritic cells (DCs) initiate and regulate the highly pathogenspecific adaptive immune responses and are central to the development of immunological memory and tolerance (11, 20)....
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851 citations
"The Capsule of Porphyromonas gingiv..." refers background in this paper
...gingivalis, an anaerobic Gram-negative member of the Cytophaga-Bacteroidetes family, belongs to a “red complex” of species associated with chronic periodontal infections (25, 43, 50)....
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