DOI:

10.37988/1811-153X_2021_1_46

Topical aspects of the chronic periodontitis immunopathogenesis (review)

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Authors

  • I.I. Antonov 1, postgraduate at the Oral and maxillofacial surgery Department
    ORCID ID: 0000-0002-2325-9010
  • V.P. Mudrov 2, 3, PhD in Medical sciences, Laboratory physician; assistant at the Medical biochemistry and immunopathology Department
    ORCID ID: 0000-0003-1129-8335
  • V.N. Nelyubin 4, PhD in Medical Sciences, leading researcher of the Medico-dental research Institute
    ORCID ID: 0000-0002-3001-9939
  • A.A. Muraev 1, PhD in Medical Sciences, full professor of the Oral and maxillofacial surgery Department
    ORCID ID: 0000-0003-3982-5512
  • 1 RUDN University, 117198, Moscow, Russia
  • 2 9th Medical and diagnostic Center of Russian Ministry of Defense, Moscow, Russia
  • 3 Russian Medical Academy of Continuous Professional Education, 125993, Moscow, Russia
  • 4 Moscow State University of Medicine and Dentistry, 127473, Moscow, Russia

Abstract

The research analysis of a number of Russian and foreign authors devoted to the study of immunopathogenesis of chronic periodontitis is presented in this study. Periodontal disease is one of the leading problems of modern dentistry. Their importance as a medical problem is determined by the high prevalence of various forms of periodontal disease in the world. Periodontitis is characterized mainly by chronic course and in the absence of timely treatment leads to such serious consequences, such as the formation of a huge focus of odontogenic infection, weakening of body reactivity, loss of teeth and alveolar bone atrophy. In 2016, serious periodontal disease, which can lead to tooth loss, became the 11th most important disease in the world. The high prevalence and constant increase in the incidence of periodontal disease among the population, the difficulties of prevention and treatment of this disease maintain a constant scientific and practical interest in finding new approaches to solving the problem. Literature data on the immunological reactivity in periodontal disease are extremely diverse and contradictory, which is noted by many domestic and foreign researchers. This can be explained by the fact that the immunological reactivity of periodontitis patients is variable: it depends on the degree of severity, phase of the disease, age and genetic predisposition of the patient, type of inflammatory reaction and a number of other circumstances. The purpose of this review was to study the current understanding of the immunopathogenesis of chronic periodontitis in terms of a whole complex of etiological pathogens.
Materials and methods.
A literature search was conducted for PubMed (www.ncbi.nlm.nih.gov), eLibrary (elibrary.ru) ScienceDirect (www.sciencedirect.com).
Results.
As a result of the analysis of the literature, the main etiological factor recognized by most authors is infectious agents: not only bacteria, but also viruses, fungi and their interaction in the process of immunopathogenesis of chronic periodontitis, as well as the immune response of the host outstrips the intensity of periodontitis flow and severity of periodontal tissue destruction. Opinion. Understanding the processes of the immune response, the formation and progression of apical periodontitis, and the identification of biomarkers of inflammation can contribute to increased knowledge of pathogenetic mechanisms, improved diagnosis, and support for various therapeutic strategies.
Conclusions.
Research on viral, fungal and bacterial periodontal infections will help to understand the clinical and biological features of periodontitis and to formulate new strategies to combat the disease. Identification and quantitative evaluation of periodontal pathogens may have a prognostic value.

Key words:

immunopathogenesis of periodontitis, periodontal diagnostics, periodontal immunology, periodontal local immunity, periodontal pathogen

For Citation

[1]
Antonov I.I., Mudrov V.P., Nelyubin V.N., Muraev A.A. Topical aspects of the chronic periodontitis immunopathogenesis (review). Clinical Dentistry (Russia).  2021; 1 (97): 46—58. DOI: 10.37988/1811-153X_2021_1_46

References

  1. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990—2016: a systematic analysis for the Global Burden of Disease Study 2016. — Lancet. — 2017; 390 (10100): 1211—59. PMID: 28919117
  2. Gomes-Filho I.S., da Cruz S.S., Trindade S.C., de Santana Passos-Soares J., Carvalho-Filho P.C., Figueiredo A.C.M.G., Lyrio A.O., Hintz A.M., Pereira M.G., Scannapieco F. Periodontitis and respiratory diseases: A systematic review with meta-analysis. — Oral Dis. — 2020; 26 (2): 439—46. PMID: 31715080
  3. Slots J. Focal infection of periodontal origin. — Periodontol 2000. — 2019; 79 (1): 233—5. PMID: 30892771
  4. Colombo A.P.V., Magalhães C.B., Hartenbach F.A.R.R., Souto R.M., da Silva-Boghossian C.M. Periodontal-disease-associated biofilm: A reservoir for pathogens of medical importance. — Microb Pathog. — 2016; 94: 27—34. PMID: 26416306
  5. Chevalier M., Ranque S., Prêcheur I. Oral fungal-bacterial biofilm models in vitro: a review. — Med Mycol. — 2018; 56 (6): 653—67. PMID: 29228383
  6. Ippolitov E.V. Monitoring of microbial biofilm formation and optimization of periodontal inflammatory diseases diagnostics: dissertation abstract. — Moscow: Sechenov University, 2016. — 49 p. (In Russ.).
  7. Chen C., Feng P., Slots J. Herpesvirus-bacteria synergistic interaction in periodontitis. — Periodontol 2000. — 2020; 82 (1): 42—64. PMID: 31850623
  8. Olsen I., Progulske-Fox A. Invasion of Porphyromonas gingivalis strains into vascular cells and tissue. — J Oral Microbiol. — 2015; 7: 28788. PMID: 26329158
  9. Carvalho-Filho P.C., Gomes-Filho I.S., Meyer R., Olczak T., Xavier M.T., Trindade S.C. Role of Porphyromonas gingivalis HmuY in immunopathogenesis of chronic periodontitis. — Mediators Inflamm. — 2016; 2016: 7465852. PMID: 27403039
  10. Zenobia C., Hajishengallis G. Porphyromonas gingivalis virulence factors involved in subversion of leukocytes and microbial dysbiosis. — Virulence. — 2015; 6 (3): 236—43. PMID: 25654623
  11. Jung Y.-J., Jun H.-K., Choi B.-K. Contradictory roles of Porphyromonas gingivalis gingipains in caspase—1 activation. — Cell Microbiol. — 2015; 17 (9): 1304—19. PMID: 25759090
  12. Nakayama M., Inoue T., Naito M., Nakayama K., Ohara N. Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp. — J Biol Chem. — 2015; 290 (8): 5190—202. PMID: 25564612
  13. Hutcherson J.A., Bagaitkar J., Nagano K., Yoshimura F., Wang H., Scott D.A. Porphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist. — Mol Oral Microbiol. — 2015; 30 (3): 242—52. PMID: 25418117
  14. Bengtsson T., Khalaf A., Khalaf H. Secreted gingipains from Porphyromonas gingivalis colonies exert potent immunomodulatory effects on human gingival fibroblasts. — Microbiol Res. — 2015; 178: 18—26. PMID: 26302843
  15. Lönn J., Ljunggren S., Klarström-Engström K., Demirel I., Bengtsson T., Karlsson H. Lipoprotein modifications by gingipains of Porphyromonas gingivalis. — J Periodontal Res. — 2018; 53 (3): 403—13. PMID: 29341140
  16. Behm C., Blufstein A., Abhari S.Y., Koch C., Gahn J., Schäffer C., Moritz A., Rausch-Fan X., Andrukhov O. Response of human mesenchymal stromal cells from periodontal tissue to LPS depends on the purity but not on the LPS source. — Mediators Inflamm. — 2020; 2020: 8704896. PMID: 32714091
  17. Olczak T., Sosicka P., Olczak M. HmuY is an important virulence factor for Porphyromonas gingivalis growth in the heme-limited host environment and infection of macrophages. — Biochem Biophys Res Commun. — 2015; 467 (4): 748—53. PMID: 26482851
  18. Trindade S.C., Olczak T., Gomes-Filho I.S., Moura-Costa L.F., Cerqueira E.M.M., Galdino-Neto M., Alves H., Carvalho-Filho P.C., Xavier M.T., Meyer R. Induction of interleukin (IL)-1β, IL-10, IL-8 and immunoglobulin G by Porphyromonas gingivalis HmuY in humans. — J Periodontal Res. — 2012; 47 (1): 27—32. PMID: 21848614
  19. Fujita Y., Nakayama M., Naito M., Yamachika E., Inoue T., Nakayama K., Iida S., Ohara N. Hemoglobin receptor protein from Porphyromonas gingivalis induces interleukin-8 production in human gingival epithelial cells through stimulation of the mitogen-activated protein kinase and NF-κB signal transduction pathways. — Infect Immun. — 2014; 82 (1): 202—11. PMID: 24126532
  20. Wang C., Hörkkö S. Natural Monoclonal Antibody to Oxidized Low-Density Lipoprotein and Aggregatibacter actinomycetemcomitans. — Methods Mol Biol. — 2017; 1643: 155—67. PMID: 28667536
  21. Konig M.F., Abusleme L., Reinholdt J., Palmer R.J., Teles R.P., Sampson K., Rosen A., Nigrovic P.A., Sokolove J., Giles J.T., Moutsopoulos N.M., Andrade F. Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. — Sci Transl Med. — 2016; 8 (369): 369ra176. PMID: 27974664
  22. Kumawat R.M., Ganvir S.M., Hazarey V.K., Qureshi A., Purohit H.J. Detection of Porphyromonas gingivalis and Treponema denticola in chronic and aggressive periodontitis patients: A comparative polymerase chain reaction study. — Contemp Clin Dent. — 2016; 7 (4): 481—6. PMID: 27994415
  23. Makino K., Takeichi O., Imai K., Inoue H., Hatori K., Himi K., Saito I., Ochiai K., Ogiso B. Porphyromonas endodontalis reactivates latent Epstein-Barr virus. — Int Endod J. — 2018; 51 (12): 1410—1419. PMID: 29858508
  24. Alyami H.M., Finoti L.S., Teixeira H.S., Aljefri A., Kinane D.F., Benakanakere M.R. Role of NOD1/NOD2 receptors in Fusobacterium nucleatum mediated NETosis. — Microb Pathog. — 2019; 131: 53—64. PMID: 30940608
  25. Ohara-Nemoto Y., Shimoyama Y., Nakasato M., Nishimata H., Ishikawa T., Sasaki M., Kimura S., Nemoto T.K. Distribution of dipeptidyl peptidase (DPP) 4, DPP5, DPP7 and DPP11 in human oral microbiota-potent biomarkers indicating presence of periodontopathic bacteria. — FEMS Microbiol Lett. — 2018; 365 (22). PMID: 30203018
  26. Groeger S., Meyle J. Oral Mucosal Epithelial Cells. — Front Immunol. — 2019; 10: 208. PMID: 30837987
  27. de Cássia Negrini T., Koo H., Arthur R.A. Candida-bacterial biofilms and host-microbe interactions in oral diseases. — Adv Exp Med Biol. — 2019; 1197: 119—41. PMID: 31732939
  28. Mergoni G., Percudani D., Lodi G., Bertani P., Manfredi M. Prevalence of Candida species in endodontic infections: Systematic review and meta-analysis. — J Endod. — 2018; 44 (11): 1616—1625.e9. PMID: 30241680
  29. Lomeli-Martinez S.M., Valentin-Goméz E., Varela-Hernández J.J., Alvarez-Zavala M., Sanchez-Reyes K., Ramos-Solano M., Cabrera-Silva R.I., Ramirez-Anguiano V.M., Lomeli-Martinez M.A., Martinez-Salazar S.Y., González-Hernández L.A., Andrade-Villanueva J.F. Candida spp. determination and Th1/Th2 mixed cytokine profile in oral samples from HIV+ patients with chronic periodontitis. — Front Immunol. — 2019; 10: 1465. PMID: 31316513
  30. Aggarwal T., Lamba A.K., Faraz F., Tandon S. Viruses: Bystanders of periodontal disease. — Microb Pathog. — 2017; 102: 54—8. PMID: 27899307
  31. Akram Z., Al-Aali K.A., Alrabiah M., Alonaizan F.A., Abduljabbar T., AlAhmari F., Javed F., Vohra F. Current weight of evidence of viruses associated with peri-implantitis and peri-implant health: A systematic review and meta-analysis. — Rev Med Virol. — 2019; 29 (3): e2042. PMID: 30901504
  32. Shatokhin A.I., Volchkova E.V. Role of herpes viruses in periodontal disease pathogenesis. — Stomatology. — 2016; 95 (2): 89—91 (In Russ.).
  33. Slots J., Slots H. Periodontal herpesvirus morbidity and treatment. — Periodontol 2000. — 2019; 79 (1): 210—20. PMID: 30892761
  34. Li F., Zhu C., Deng F.-Y., Wong M.C.M., Lu H.-X., Feng X.-P. Herpesviruses in etiopathogenesis of aggressive periodontitis: A meta-analysis based on case-control studies. — PLoS One. — 2017; 12 (10): e0186373. PMID: 29036216
  35. Watanabe N., Nodomi K., Koike R., Kato A., Takeichi O., Kotani A.I., Kaneko T., Sakagami H., Takei M., Ogata Y., Sato S., Imai K. EBV LMP1 in gingival epithelium potentially contributes to human chronic periodontitis via inducible IL8 production. — In Vivo. — 2019; 33 (6): 1793—800. PMID: 31662504
  36. Muzammil, Jayanthi D., Faizuddin M., Ahamadi H.M.N. Association of interferon lambda-1 with herpes simplex viruses-1 and -2, Epstein-Barr virus, and human cytomegalovirus in chronic periodontitis. — J Investig Clin Dent. — 2017; 8 (2). PMID: 26677065
  37. Santos-Lima E.K.N., Oliveira Y.A., Santos R.P.B., Sampaio G.P., Pimentel A.C.M., Carvalho-Filho P.C., Moura-Costa L.F., Olczak T., Gomes-Filho I.S., Meyer R.J., Xavier M.T., Trindade S.C. Production of interferon-gamma, interleukin-6, and interleukin-1β by human peripheral blood mononuclear cells stimulated with novel lys-gingipain synthetic peptides. — J Periodontol. — 2019; 90 (9): 993—1001. PMID: 30868592
  38. de Sousa Rodrigues P.M., Teixeira A.L., Kustner E.C., Medeiros R. Are herpes virus associated to aggressive periodontitis? A review of literature. — J Oral Maxillofac Pathol. — 2015; 19 (3): 348—55. PMID: 26980964
  39. Himi K., Takeichi O., Imai K., Hatori K., Tamura T., Ogiso B. Epstein-Barr virus reactivation by persistent apical periodontal pathogens. — Int Endod J. — 2020; 53 (4): 492—505. PMID: 31730263
  40. Chowdhry R., Singh N., Sahu D.K., Tripathi R.K., Mishra A., Singh A., Mukerjee I., Lal N., Bhatt M.L.B., Kant R. Dysbiosis and variation in predicted functions of the granulation tissue microbiome in HPV positive and negative severe chronic periodontitis. — Biomed Res Int. — 2019; 2019: 8163591. PMID: 31111067
  41. Abbas A.A., Taylor L.J., Dothard M.I., Leiby J.S., Fitzgerald A.S., Khatib L.A., Collman R.G., Bushman F.D. Redondoviridae, a family of small, circular DNA viruses of the human oro-respiratory tract associated with periodontitis and critical illness. — Cell Host Microbe. — 2019; 25 (5): 719—729.e4. PMID: 31071295
  42. Pólvora T.L.S., Nobre Á.V.V., Tirapelli C., Jr M.T., de Macedo L.D., Santana R.C., Pozzetto B., Lourenço A.G., Motta A.C.F. Relationship between human immunodeficiency virus (HIV—1) infection and chronic periodontitis. — Expert Rev Clin Immunol. — 2018; 14 (4): 315—27. PMID: 29595347
  43. Cavalla F., Letra A., Silva R.M., Garlet G.P. Determinants of periodontal/periapical lesion stability and progression. — J Dent Res. — 2021; 100 (1): 29—36. PMID: 32866421
  44. Cardoso E.M., Reis C., Manzanares-Céspedes M.C. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. — Postgrad Med. — 2018; 130 (1): 98—104. PMID: 29065749
  45. Moutsopoulos N.M., Konkel J.E. Tissue-specific immunity at the oral mucosal barrier. — Trends Immunol. — 2018; 39 (4): 276—87. PMID: 28923364
  46. Meyle J., Chapple I. Molecular aspects of the pathogenesis of periodontitis. — Periodontol 2000. — 2015; 69 (1): 7—17. PMID: 26252398
  47. Varanat M., Haase E.M., Kay J.G., Scannapieco F.A. Activation of the TREM-1 pathway in human monocytes by periodontal pathogens and oral commensal bacteria. — Mol Oral Microbiol. — 2017; 32 (4): 275—87. PMID: 27448788
  48. Yu X., Hu Y., Freire M., Yu P., Kawai T., Han X. Role of toll-like receptor 2 in inflammation and alveolar bone loss in experimental peri-implantitis versus periodontitis. — J Periodontal Res. — 2018; 53 (1): 98—106. PMID: 28872184
  49. Araujo-Pires A.C., Francisconi C.F., Biguetti C.C., Cavalla F., Aranha A.M.F., Letra A., Trombone A.P.F., Faveri M., Silva R.M., Garlet G.P. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. — J Appl Oral Sci. — 2014; 22 (4): 336—46. PMID: 25141207
  50. Braz-Silva P.H., Bergamini M.L., Mardegan A.P., De Rosa C.S., Hasseus B., Jonasson P. Inflammatory profile of chronic apical periodontitis: a literature review. — Acta Odontol Scand. — 2019; 77 (3): 173—80. PMID: 30585523
  51. Arul D., Rao S. Isolation of Naturally Induced T-regulatory Cells in Gingival Tissues of Healthy Human Subjects and Subjects with Gingivitis and Chronic Periodontitis. — Cureus. — 2019; 11 (3): e4283. PMID: 31183266
  52. da Motta R.J.G., Almeida L.Y., Villafuerte K.R.V., Ribeiro-Silva A., León J.E., Tirapelli C. FOXP3+ and CD25+ cells are reduced in patients with stage IV, grade C periodontitis: A comparative clinical study. — J Periodontal Res. — 2020; 55 (3): 374—80. PMID: 31876956
  53. Stadler A.F., Angst P.D.M., Arce R.M., Gomes S.C., Oppermann R.V., Susin C. Gingival crevicular fluid levels of cytokines/chemokines in chronic periodontitis: a meta-analysis. — J Clin Periodontol. — 2016; 43 (9): 727—45. PMID: 27027257
  54. Hovav A.H., Wilharm A., Barel O., Prinz I. Development and function of γδT cells in the oral mucosa. — J Dent Res. — 2020; 99 (5): 498—505. PMID: 32091949
  55. Mudrov V.P., Mandiev M.S., Fomenko I.S., Ivanov S.Iu., Lolokova N.V., Nelyubin V.N. Cytokine regulation of inflammation and bacterial-viral co-infection in periodontal tissues with periodontitis. — Citokines and Inflammation. — 2016; 2: 212—5 (In Russ.).
  56. Bilichodmath S., Nair S.K., Bilichodmath R., Mangalekar S.B. mRNA expression of IFN-λs in the gingival tissue of patients with chronic or aggressive periodontitis: A polymerase chain reaction study. — J Periodontol. — 2018; 89 (7): 867—74. PMID: 29717481
  57. da Luz F.A.C., Oliveira A.P.L., Borges D., Brígido P.C., Silva M.J.B. The physiopathological role of IL—33: new highlights in bone biology and a proposed role in periodontal disease. — Mediators Inflamm. — 2014; 2014: 342410. PMID: 24692848
  58. Malcolm J., Awang R.A., Oliver-Bell J., Butcher J.P., Campbell L., Planell A.A., Lappin D.F., Fukada S.Y., Nile C.J., Liew F.Y., Culshaw S. IL-33 exacerbates periodontal disease through induction of RANKL. — J Dent Res. — 2015; 94 (7): 968—75. PMID: 25808546
  59. Tada H., Matsuyama T., Nishioka T., Hagiwara M., Kiyoura Y., Shimauchi H., Matsushita K. Porphyromonas gingivalis gingipain-dependently enhances IL-33 production in human gingival epithelial cells. — PLoS One. — 2016; 11 (4): e0152794. PMID: 27058037
  60. Taiete T., Monteiro M.F., Casati M.Z., Vale H.F., Ambosano G.M.B., Nociti F.H., Sallum E.A., Casarin R.C.V. Local IL-10 level as a predictive factor in generalized aggressive periodontitis treatment response. — Scand J Immunol. — 2019; 90 (6): e12816. PMID: 31448837
  61. Moretti S., Bartolommei L., Galosi C., Renga G., Oikonomou V., Zamparini F. et al. Fine-tuning of Th17 cytokines in periodontal disease by IL-10. — J Dent Res. — 2015; 94 (9): 1267—75. PMID: 26092379
  62. Yoshinaka K., Shoji N., Nishioka T., Sugawara Y., Hoshino T., Sugawara S., Sasano T. Increased interleukin-18 in the gingival tissues evokes chronic periodontitis after bacterial infection. — Tohoku J Exp Med. — 2014; 232 (3): 215—22. PMID: 24646956
  63. Chitrapriya M.N., Rao S.R., Lavu V. Interleukin-17 and interleukin-18 levels in different stages of inflammatory periodontal disease. — J Indian Soc Periodontol. — 2015; 19 (1): 14—7. PMID: 25810587
  64. Bunte K., Beikler T. Th17 Cells and the IL-23/IL-17 axis in the pathogenesis of periodontitis and immune-mediated inflammatory diseases. — Int J Mol Sci. — 2019; 20 (14): 3394. PMID: 31295952
  65. Luo Y., Peng X., Duan D., Liu C., Xu X., Zhou X. Epigenetic regulations in the pathogenesis of periodontitis. — Curr Stem Cell Res Ther. — 2018; 13 (2): 144—50. PMID: 28721820
  66. Lina S., Lihong Q., Di Y., Bo Y., Xiaolin L., Jing M. microRNA-146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis. — J Cell Biochem. — 2019; 120 (1): 645—57. PMID: 30125982
  67. Vigueras S.H., Zúñiga M.D., Jané-Salas E., Navarrete L.S., Segura-Egea J.J., Velasco-Ortega E., López-López J. Viruses in pulp and periapical inflammation: a review. — Odontology. — 2016; 104 (2): 184—91. PMID: 25796386
  68. Dutzan N., Abusleme L. T Helper 17 Cells as pathogenic drivers of periodontitis. — Adv Exp Med Biol. — 2019; 1197: 107—117. PMID: 31732938

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March 1, 2021