Journal of Clinical Medicine

Editorial

3 pages, 178 KiB

Open AccessEditorial

Comment from the Editor to the Special Issue: “Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation”

by Jan Oscarsson and Anders Johansson

J. Clin. Med. 2019, 8(10), 1706; https://doi.org/10.3390/jcm8101706 - 16 Oct 2019

Cited by 6 | Viewed by 2290

Abstract

The human oral cavity contains a large number of different microbial habitats. When microbes from the oral indigenous flora colonize the interspace between the tooth and the connective tissue, they induce an inflammatory response. If the microbes are in sufficient numbers, and release [...] Read more.

The human oral cavity contains a large number of different microbial habitats. When microbes from the oral indigenous flora colonize the interspace between the tooth and the connective tissue, they induce an inflammatory response. If the microbes are in sufficient numbers, and release components that cause an imbalance in the host inflammatory response, degenerative processes in the surrounding tissues are induced, ultimately resulting in periodontal disease. The disease progress depends on bacterial load, the composition of the microbial community, and host genetic factors. The two most studied periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans express virulence factors, including proteases and exotoxins. Periodontal infections are also linked to the risk pattern of several systemic diseases. We would like to shed light on the mechanisms behind periodontitis and the associations of periodontal infections with systemic inflammation. Seven articles are included in this Special Issue and cover several pathogenic processes in the periodontal infection with capacity to cause imbalance in the host response. Highlights from each of the published papers are summarized and discussed below. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

Research

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14 pages, 2781 KiB

Open AccessArticle

TREM-1 Is Upregulated in Experimental Periodontitis, and Its Blockade Inhibits IL-17A and RANKL Expression and Suppresses Bone loss

by Nagihan Bostanci, Toshiharu Abe, Georgios N. Belibasakis and George Hajishengallis

J. Clin. Med. 2019, 8(10), 1579; https://doi.org/10.3390/jcm8101579 - 1 Oct 2019

Cited by 25 | Viewed by 3706

Abstract

Aim: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a modifier of local and systemic inflammation. There is clinical evidence implicating TREM-1 in the pathogenesis of periodontitis. However, a cause-and-effect relationship has yet to be demonstrated, as is the underlying mechanism. The aim [...] Read more.

Aim: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a modifier of local and systemic inflammation. There is clinical evidence implicating TREM-1 in the pathogenesis of periodontitis. However, a cause-and-effect relationship has yet to be demonstrated, as is the underlying mechanism. The aim of this study was to elucidate the role of TREM-1 using the murine ligature-induced periodontitis model. Methods: A synthetic antagonistic LP17 peptide or sham control was microinjected locally into the palatal gingiva of the ligated molar teeth. Results: Mice treated with the LP17 inhibitor developed significantly less bone loss as compared to sham-treated mice, although there were no differences in total bacterial load on the ligatures. To elucidate the impact of LP17 on the host response, we analyzed the expression of a number of immune-modulating genes. The LP17 peptide altered the expression of 27/92 genes ≥ two-fold, but only interleukin (IL)-17A was significantly downregulated (4.9-fold). Importantly, LP17 also significantly downregulated the receptor activator of nuclear factor kappa-B-ligand (RANKL) to osteoprotegerin (OPG) ratio that drives osteoclastic bone resorption in periodontitis. Conclusion: Our findings show for the first time that TREM-1 regulates the IL-17A-RANKL/OPG axis and bone loss in experimental periodontitis, and its therapeutic blockade may pave the way to a novel treatment for human periodontitis. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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16 pages, 1168 KiB

Open AccessArticle

Saliva and Serum Immune Responses in Apical Periodontitis

by Milla Pietiäinen, John M. Liljestrand, Ramin Akhi, Kåre Buhlin, Anders Johansson, Susanna Paju, Aino Salminen, Päivi Mäntylä, Juha Sinisalo, Leo Tjäderhane, Sohvi Hörkkö and Pirkko J. Pussinen

J. Clin. Med. 2019, 8(6), 889; https://doi.org/10.3390/jcm8060889 - 21 Jun 2019

Cited by 18 | Viewed by 4945

Abstract

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive [...] Read more.

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01–8.33) and 4.91 (2.48–9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48–2.97)), serum IgG to bacterial antigens (4.66 (1.22–10.1)), and Gram-negative subgingival species (1.98 (1.16–3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05–21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis—a putative risk factor for systemic diseases. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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Review

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19 pages, 1165 KiB

Open AccessReview

Importance of Virulence Factors for the Persistence of Oral Bacteria in the Inflamed Gingival Crevice and in the Pathogenesis of Periodontal Disease

by Gunnar Dahlen, Amina Basic and Johan Bylund

J. Clin. Med. 2019, 8(9), 1339; https://doi.org/10.3390/jcm8091339 - 29 Aug 2019

Cited by 94 | Viewed by 11152

Abstract

Periodontitis is a chronic inflammation that develops due to a destructive tissue response to prolonged inflammation and a disturbed homeostasis (dysbiosis) in the interplay between the microorganisms of the dental biofilm and the host. The infectious nature of the microbes associated with periodontitis [...] Read more.

Periodontitis is a chronic inflammation that develops due to a destructive tissue response to prolonged inflammation and a disturbed homeostasis (dysbiosis) in the interplay between the microorganisms of the dental biofilm and the host. The infectious nature of the microbes associated with periodontitis is unclear, as is the role of specific bacterial species and virulence factors that interfere with the host defense and tissue repair. This review highlights the impact of classical virulence factors, such as exotoxins, endotoxins, fimbriae and capsule, but also aims to emphasize the often-neglected cascade of metabolic products (e.g., those generated by anaerobic and proteolytic metabolism) that are produced by the bacterial phenotypes that survive and thrive in deep, inflamed periodontal pockets. This metabolic activity of the microbes aggravates the inflammatory response from a low-grade physiologic (homeostatic) inflammation (i.e., gingivitis) into more destructive or tissue remodeling processes in periodontitis. That bacteria associated with periodontitis are linked with a number of systemic diseases of importance in clinical medicine is highlighted and exemplified with rheumatoid arthritis, The unclear significance of a number of potential “virulence factors” that contribute to the pathogenicity of specific bacterial species in the complex biofilm–host interaction clinically is discussed in this review. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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24 pages, 341 KiB

Open AccessReview

Rheumatoid Arthritis-Associated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans

by Eduardo Gómez-Bañuelos, Amarshi Mukherjee, Erika Darrah and Felipe Andrade

J. Clin. Med. 2019, 8(9), 1309; https://doi.org/10.3390/jcm8091309 - 26 Aug 2019

Cited by 87 | Viewed by 10243

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by immune-mediated damage of synovial joints and antibodies to citrullinated antigens. Periodontal disease, a bacterial-induced inflammatory disease of the periodontium, is commonly observed in RA and has implicated periodontal pathogens as potential [...] Read more.

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by immune-mediated damage of synovial joints and antibodies to citrullinated antigens. Periodontal disease, a bacterial-induced inflammatory disease of the periodontium, is commonly observed in RA and has implicated periodontal pathogens as potential triggers of the disease. In particular, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans have gained interest as microbial candidates involved in RA pathogenesis by inducing the production of citrullinated antigens. Here, we will discuss the clinical and mechanistic evidence surrounding the role of these periodontal bacteria in RA pathogenesis, which highlights a key area for the treatment and preventive interventions in RA. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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Graphical abstract

12 pages, 786 KiB

Open AccessReview

Periodontitis: A Multifaceted Disease of Tooth-Supporting Tissues

by Eija Könönen, Mervi Gursoy and Ulvi Kahraman Gursoy

J. Clin. Med. 2019, 8(8), 1135; https://doi.org/10.3390/jcm8081135 - 31 Jul 2019

Cited by 457 | Viewed by 32358

Abstract

Periodontitis is an infection-driven inflammatory disease in which the composition of biofilms plays a significant role. Dental plaque accumulation at the gingival margin initiates an inflammatory response that, in turn, causes microbial alterations and may lead to drastic consequences in the periodontium of [...] Read more.

Periodontitis is an infection-driven inflammatory disease in which the composition of biofilms plays a significant role. Dental plaque accumulation at the gingival margin initiates an inflammatory response that, in turn, causes microbial alterations and may lead to drastic consequences in the periodontium of susceptible individuals. Chronic inflammation affects the gingiva and can proceed to periodontitis, which characteristically results in irreversible loss of attachment and alveolar bone. Periodontitis appears typically in adult-aged populations, but young individuals can also experience it and its harmful outcome. Advanced disease is the major cause of tooth loss in adults. In addition, periodontitis is associated with many chronic diseases and conditions affecting general health. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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9 pages, 524 KiB

Open AccessReview

Next Generation Sequencing Discoveries of the Nitrate-Responsive Oral Microbiome and Its Effect on Vascular Responses

by Melissa M. Grant and Daniel Jönsson

J. Clin. Med. 2019, 8(8), 1110; https://doi.org/10.3390/jcm8081110 - 26 Jul 2019

Cited by 12 | Viewed by 8564

Abstract

Cardiovascular disease is a worldwide human condition which has multiple underlying contributing factors: one of these is long-term increased blood pressure—hypertension. Nitric oxide (NO) is a small nitrogenous radical species that has a number of physiological functions including vasodilation. It can be produced [...] Read more.

Cardiovascular disease is a worldwide human condition which has multiple underlying contributing factors: one of these is long-term increased blood pressure—hypertension. Nitric oxide (NO) is a small nitrogenous radical species that has a number of physiological functions including vasodilation. It can be produced enzymatically through host nitric oxide synthases and by an alternative nitrate–nitrite–NO pathway from ingested inorganic nitrate. It was discovered that this route relies on the ability of the oral microbiota to reduce nitrate to nitrite and NO. Next generation sequencing has been used over the past two decades to gain deeper insight into the microbes involved, their location and the effect of their removal from the oral cavity. This review article presents this research and comments briefly on future directions. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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12 pages, 1222 KiB

Open AccessReview

Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response

by Jan Oscarsson, Rolf Claesson, Mark Lindholm, Carola Höglund Åberg and Anders Johansson

J. Clin. Med. 2019, 8(7), 1079; https://doi.org/10.3390/jcm8071079 - 22 Jul 2019

Cited by 37 | Viewed by 7828

Abstract

Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. [...] Read more.

Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. Aggregatibacter actinomycetemcomitans is a facultative anaerobic Gram-negative bacterium associated with such cellular and molecular mechanisms associated with the pathogenesis of periodontitis. In the present review, we outline virulence mechanisms that help the bacterium to escape the host response. These properties include invasiveness, secretion of exotoxins, serum resistance, and release of outer membrane vesicles. Virulence properties of A. actinomycetemcomitans that can contribute to treatment resistance in the infected individuals and upon translocation to the circulation, also induce pathogenic mechanisms associated with several systemic diseases. Full article

(This article belongs to the Special Issue Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation)

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