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Frontiers in Immunology 2023Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to () and RA has been...
BACKGROUND
Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to () and RA has been established, but data on saliva antibodies to in RA are lacking. We evaluated antibodies to in serum and saliva in two Swedish RA studies as well as their association with RA, periodontitis, antibodies to citrullinated proteins (ACPA), and RA disease activity.
METHODS
The SARA (secretory antibodies in RA) study includes 196 patients with RA and 101 healthy controls. The Karlskrona RA study includes 132 patients with RA ≥ 61 years of age, who underwent dental examination. Serum Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies and saliva IgA antibodies to the -specific Arg-specific gingipain B (RgpB) were measured in patients with RA and controls.
RESULTS
The level of saliva IgA anti-RgpB antibodies was significantly higher among patients with RA than among healthy controls in multivariate analysis adjusted for age, gender, smoking, and IgG ACPA (p = 0.022). Saliva IgA anti-RgpB antibodies were associated with RA disease activity in multivariate analysis (p = 0.036). Anti-RgpB antibodies were not associated with periodontitis or serum IgG ACPA.
CONCLUSION
Patients with RA had higher levels of saliva IgA anti-RgpB antibodies than healthy controls. Saliva IgA anti-RgpB antibodies may be associated with RA disease activity but were not associated with periodontitis or serum IgG ACPA. Our results indicate a local production of IgA anti-RgpB in the salivary glands that is not accompanied by systemic antibody production.
Topics: Humans; Sweden; Porphyromonas gingivalis; Saliva; Peptides, Cyclic; Arthritis, Rheumatoid; Immunoglobulin G; Gingipain Cysteine Endopeptidases; Periodontitis; Immunoglobulin A
PubMed: 37325636
DOI: 10.3389/fimmu.2023.1183194 -
Frontiers in Cellular and Infection... 2023is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. expresses a variety of virulence factors that disrupt innate... (Review)
Review
is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. expresses a variety of virulence factors that disrupt innate and adaptive immunity, allowing to survive and multiply in the host and destroy periodontal tissue. In addition to periodontal disease, is also associated with systemic diseases, of which insulin resistance is an important pathological basis. causes a systemic inflammatory response, disrupts insulin signaling pathways, induces pancreatic β-cell hypofunction and reduced numbers, and causes decreased insulin sensitivity leading to insulin resistance (IR). In this paper, we systematically review the studies on the mechanism of insulin resistance induced by , discuss the association between and systemic diseases based on insulin resistance, and finally propose relevant therapeutic approaches. Overall, through a systematic review of the mechanisms related to systemic diseases caused by through insulin resistance, we hope to provide new insights for future basic research and clinical interventions for related systemic diseases.
Topics: Humans; Porphyromonas gingivalis; Insulin Resistance; Base Composition; RNA, Ribosomal, 16S; Phylogeny; Sequence Analysis, DNA; Insulin
PubMed: 37520442
DOI: 10.3389/fcimb.2023.1209381 -
Medicina (Kaunas, Lithuania) Nov 2023: More than a billion people worldwide suffer from chronic periodontitis. The primary etiological factor of periodontal diseases is dental plaque and the bacteria it... (Review)
Review
: More than a billion people worldwide suffer from chronic periodontitis. The primary etiological factor of periodontal diseases is dental plaque and the bacteria it contains, particularly , , , , and . Zinc, owing to its antibacterial properties, can be employed in periodontology. The objective of this review was to analyze scientific literature that examines the effects of zinc on periopathogens. : A systematic review protocol of scientific literature was designed following PRISMA recommendations. Data search was conducted in PubMed, Web of Science, and ScienceDirect databases. Full-text articles in English that examine the effects of zinc on periopathogens and were published between 2011 and 2021 were included. Fifteen articles were included in the analysis based on inclusion criteria. ZnO exhibited antibacterial activity against and ( < 0.001). The minimum inhibitory concentration against was 10 μg/mL. ZnO demonstrated a significant antibacterial effect, as evidenced by inhibition zones of 15.10 mm for , 13.36 mm for , 12.98 mm for , and 14.01 mm for Zn (II)-based polymers inhibited the and genes of . Titanium dental implants coated with ZnO effectively disrupted the cell walls of and . ZnO inhibited the growth of within 2 h and the growth of and within 3 h. ZnO exhibited nontoxic effects, and concentrations up to 0.8 mg/L increased cell survival rates by up to 90%. The analysis of the literature confirms the antibacterial action of zinc against periodontal pathogenic bacteria. At low concentrations, these substances do not exhibit cytotoxic effects on fibroblasts.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Chronic Periodontitis; Organic Chemicals; Porphyromonas gingivalis; Systematic Reviews as Topic; Zinc; Zinc Oxide
PubMed: 38138191
DOI: 10.3390/medicina59122088 -
Trends in Microbiology Jan 2021Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of... (Review)
Review
Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of periodontitis. Transposon sequencing has been employed to define the core essential genome of this bacterium and genes conditionally essential in multiple environments - abscess formation; epithelial colonization; and cigarette smoke toxin exposure; as well as to elucidate genes required for iron acquisition and a functional type 9 secretion system. Validated and predicted protein catabolism genes identified include a combination of established virulence factors and a larger set of seemingly more mundane proteolytic genes. The functions and relevance of genes that share essentiality in multiple disease-relevant conditions are examined. These common stress-related genes may represent particularly attractive therapeutic targets for the control of P. gingivalis infections.
Topics: Animals; Bacterial Proteins; Bacteroidaceae Infections; Genes, Essential; Humans; Porphyromonas gingivalis; Virulence Factors
PubMed: 33071035
DOI: 10.1016/j.tim.2020.09.002 -
Frontiers in Immunology 2022() is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. has recently been detected in rheumatoid... (Review)
Review
() is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. has recently been detected in rheumatoid arthritis (RA), cardiovascular disease, and tumors, as well as Alzheimer's disease (AD), and the presence of in these diseases are correlated with poor prognosis. Macrophages are major innate immune cells which modulate immune responses against pathogens, however, multiple bacteria have evolved abilities to evade or even subvert the macrophages' immune response, in which subsequently promote the diseases' initiation and progression. as a keystone pathogen of periodontitis has received increasing attention for the onset and development of systemic diseases. induces macrophage polarization and inflammasome activation. It also causes immune response evasion which plays important roles in promoting inflammatory diseases, autoimmune diseases, and tumor development. In this review, we summarize recent discoveries on the interaction of and macrophages in relevant disease development and progression, such as periodontitis, atherosclerosis, RA, AD, and cancers, aiming to provide an in-depth mechanistic understanding of this interaction and potential therapeutic strategies.
Topics: Arthritis, Rheumatoid; Humans; Inflammasomes; Macrophage Activation; Macrophages; Periodontitis; Porphyromonas gingivalis
PubMed: 35967399
DOI: 10.3389/fimmu.2022.952040 -
Journal of Integrative Neuroscience Aug 2023Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis...
BACKGROUND
Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis and major depression (MD), the biological mechanisms by which periodontitis instigates MD are unknown. We investigated whether a systemic administration of lipopolysaccharide (LPS) from (), a major Gram-negative pathogen of periodontitis, causes depressive-like behavior and glial activation in the hippocampus and the prefrontal cortex (PFC), which are MD-related brain regions.
MATERIALS AND METHODS
Eight-week-old male Sprague Dawley rats were randomly divided into a behavioral test group and an immunohistochemistry group. The rats in each group were further assigned to the sham injection (saline) and -lipopolysaccharide (-LPS) injection protocols. The rats received an intraperitoneal injection of saline or -LPS with gradually increasing doses (day 1: 0.5, day 2: 0.5, day 3: 0.75, day 4: 0.75, day 5: 1.0, day 6: 1.0, and day 7: 1.0 mg/kg of body weight) for seven consecutive days. After the systemic administration, the behavior test group underwent the forced swimming test (FST) and Y-maze test. For the immunohistochemistry group, we quantified the immunoreactivity for microglial Iba-1 (ionized calcium-binding adapter molecule 1) and astrocytic glial fibrillary acidic protein (GFAP) in the hippocampus (dentate gyrus [DG], cornu ammonis [CA1 and CA3]) and PFC (prelimbic [PrL] and the infralimbic [IL]) areas.
RESULTS
The FST immobility time in the -LPS group was significantly longer than that in the sham group. In the Y-maze test, a significant decline in spontaneous alternation behavior was observed in the -LPS group compared to the sham group. The peripheral administration of -LPS significantly increased the immunoreactivity for Iba-1 in the CA3 and PrL. -LPS injection significantly increased the immunoreactivity for GFAP in the DG, CA1, and CA3.
CONCLUSIONS
The major result of this study is that a repeated systemic administration of -LPS caused depressive-like behavior and both microglial and astrocytic activation in rats. This finding may comprise biological evidence of a causal relationship between periodontitis and MD.
Topics: Male; Rats; Animals; Rats, Sprague-Dawley; Lipopolysaccharides; Porphyromonas gingivalis; Depressive Disorder, Major; Hippocampus
PubMed: 37735127
DOI: 10.31083/j.jin2205120 -
Periodontology 2000 Jun 2022Extensive research in humans and animal models has begun to unravel the complex mechanisms that drive the immunopathogenesis of periodontitis. Neutrophils mount an early... (Review)
Review
Extensive research in humans and animal models has begun to unravel the complex mechanisms that drive the immunopathogenesis of periodontitis. Neutrophils mount an early and rapid response to the subgingival oral microbiome, producing destructive enzymes to kill microbes. Chemokines and cytokines are released that attract macrophages, dendritic cells, and T cells to the site. Dendritic cells, the focus of this review, are professional antigen-presenting cells on the front line of immune surveillance. Dendritic cells consist of multiple subsets that reside in the epithelium, connective tissues, and major organs. Our work in humans and mice established that myeloid dendritic cells are mobilized in periodontitis. This occurs in lymphoid and nonlymphoid oral tissues, in the bloodstream, and in response to Porphyromonas gingivalis. Moreover, the dendritic cells mature in situ in gingival lamina propria, forming immune conjugates with cluster of differentiation (CD) 4+ T cells, called oral lymphoid foci. At such foci, the decisions are made as to whether to promote bone destructive T helper 17 or bone-sparing regulatory T cell responses. Interestingly, dendritic cells lack potent enzymes and reactive oxygen species needed to kill and degrade endocytosed microbes. The keystone pathogen P. gingivalis exploits this vulnerability by invading dendritic cells in the tissues and peripheral blood using its distinct fimbrial adhesins. This promotes pathogen dissemination and inflammatory disease at distant sites, such as atherosclerotic plaques. Interestingly, our recent studies indicate that such P. gingivalis-infected dendritic cells release nanosized extracellular vesicles called exosomes, in higher numbers than uninfected dendritic cells do. Secreted exosomes and inflammasome-related cytokines are a key feature of the senescence-associated secretory phenotype. Exosomes communicate in paracrine with neighboring stromal cells and immune cells to promote and amplify cellular senescence. We have shown that dendritic cell-derived exosomes can be custom tailored to target and reprogram specific immune cells responsible for inflammatory bone loss in mice. The long-term goal of these immunotherapeutic approaches, ongoing in our laboratory and others, is to promote human health and longevity.
Topics: Alveolar Bone Loss; Animals; Cytokines; Dendritic Cells; Disease Susceptibility; Humans; Immunotherapy; Mice; Periodontitis; Porphyromonas gingivalis
PubMed: 35244951
DOI: 10.1111/prd.12428 -
Frontiers in Immunology 2022Aging is a gradual and progressive deterioration of integrity across multiple organ systems that negatively affects gingival wound healing. The cellular responses... (Review)
Review
Aging is a gradual and progressive deterioration of integrity across multiple organ systems that negatively affects gingival wound healing. The cellular responses associated with wound healing, such as collagen synthesis, cell migration, proliferation, and collagen contraction, have been shown to be lower in gingival fibroblasts (the most abundant cells from the connective gingival tissue) in aged donors than young donors. Cellular senescence is one of the hallmarks of aging, which is characterized by the acquisition of a senescence-associated secretory phenotype that is characterized by the release of pro-inflammatory cytokines, chemokines, growth factors, and proteases which have been implicated in the recruitment of immune cells such as neutrophils, T cells and monocytes. Moreover, during aging, macrophages show altered acquisition of functional phenotypes in response to the tissue microenvironment. Thus, inflammatory and resolution macrophage-mediated processes are impaired, impacting the progression of periodontal disease. Interestingly, salivary antimicrobial peptides, such as histatins, which are involved in various functions, such as antifungal, bactericidal, enamel-protecting, angiogenesis, and re-epithelization, have been shown to fluctuate with aging. Several studies have associated the presence of , a key pathogen related to periodontitis and apical periodontitis, with the progression of Alzheimer's disease, as well as gut, esophageal, and gastric cancers. Moreover, herpes simplex virus types 1 and 2 have been associated with the severity of periodontal disease, cardiovascular complications, and nervous system-related pathologies. This review encompasses the effects of aging on periodontal tissues, how and HSV infections could favor periodontitis and their relationship with other pathologies.
Topics: Humans; Gingiva; Porphyromonas gingivalis; Periodontium; Periodontitis; Periodontal Diseases
PubMed: 36341447
DOI: 10.3389/fimmu.2022.1044334 -
Frontiers in Immunology 2024There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health.... (Review)
Review
There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health. Disruptions in the commensal flora can lead to oral diseases, while systemic illnesses can also impact the oral cavity, resulting in the development of oral diseases and disorders. and , known as pathogenic bacteria associated with periodontitis, play a crucial role in linking periodontitis to accompanying systemic diseases. In periodontal tissues, these bacteria, along with their virulence factors, can excessively activate the host immune system through local diffusion, lymphatic circulation, and blood transmission. This immune response disruption contributes to an imbalance in osteoimmune mechanisms, alveolar bone resorption, and potential systemic inflammation. To restore local homeostasis, a deeper understanding of microbiota-host interactions and the immune network phenotype in local tissues is imperative. Defining the immune network phenotype in periodontal tissues offers a promising avenue for investigating the complex characteristics of oral plaque biofilms and exploring the potential relationship between periodontitis and associated systemic diseases. This review aims to provide an overview of the mechanisms underlying - and -induced alveolar bone resorption, as well as the immunophenotypes observed in host periodontal tissues during pathological conditions.
Topics: Humans; Periodontitis; Alveolar Bone Loss; Porphyromonas gingivalis; Inflammation; Fusobacterium nucleatum
PubMed: 38455060
DOI: 10.3389/fimmu.2024.1254516 -
International Journal of Environmental... Nov 2022The implementation of adjunctive antibiotics has been recommended for the therapy of peri-implantitis (PI). In this review, antibiotic resistance patterns in PI patients... (Review)
Review
The implementation of adjunctive antibiotics has been recommended for the therapy of peri-implantitis (PI). In this review, antibiotic resistance patterns in PI patients were assessed. A systematic scoping review of observational studies and trials was established in conjunction with the PRISMA extension for scoping reviews. The SCOPUS, PubMed/MEDLINE, EMBASE, SCIELO, Web of Science, and LILACS databases were reviewed along with the gray literature. The primary electronic examination produced 139 investigations. Finally, four observational studies met the selection criteria. These studies evaluated 214 implants in 168 patients. and mainly presented high resistance to tetracycline, metronidazole, and erythromycin in PI patients. Similarly, was also highly resistant to clindamycin and doxycycline. Other microorganisms such as , , and also presented significant levels of resistance to other antibiotics including amoxicillin, azithromycin, and moxifloxacin. However, most microorganisms did not show resistance to the combination amoxicillin metronidazole. Although the management of adjunctive antimicrobials in the therapy of PI is controversial, in this review, the resistance of relevant microorganisms to antibiotics used to treat PI, and usually prescribed in dentistry, was observed. Clinicians should consider the antibiotic resistance demonstrated in the treatment of PI patients and its public health consequences.
Topics: Humans; Peri-Implantitis; Aggregatibacter actinomycetemcomitans; Drug Resistance, Microbial; Fusobacterium nucleatum; Porphyromonas gingivalis; Amoxicillin; Metronidazole; Anti-Bacterial Agents
PubMed: 36497685
DOI: 10.3390/ijerph192315609