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Review Articles

Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

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Article: 33029 | Received 31 Jul 2016, Accepted 21 Oct 2016, Published online: 22 Nov 2016

References

  • Seymour GJ, Ford PJ, Cullinan MP, Leishman S, Yamazaki K. Relationship between periodontal infections and systemic disease. Clin Microbiol. 2007; 13(Suppl 4): 3–10.
  • Hajishengallis G, Darveau RP, Curtis MA. The keystone pathogen hypothesis. Nat Rev Microbiol. 2012; 10: 717–25. doi: http://dx.doi.org/10.1038/nrmicro2873.
  • How KY, Song KP, Chan KG. Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol. 2016; 7: 53. doi: http://dx.doi.org/10.3389/fmicb.2016.00053.
  • Hajishengallis G. Immune evasion strategies of Porphyromonas gingivalis. J Oral Biosci. 2011; 53: 233–40. doi: http://dx.doi.org/10.2330/joralbiosci.53.233.
  • Olsen I, Yilmaz Ö.Modulation of inflammasome activity by Porphyromonas gingivalis in periodontitis and associated systemic diseases. J Oral Microbiol. 2016; 8: 30385. doi: http://dx.doi.org/10.3402/jom.v8.30385.
  • Olsen I, Singhrao SK. Inflammasome involvement in Alzheimer’s disease. J Alzheimers Dis. 2016; 54: 45–53.
  • Olsen I, Hajishengallis G. Major neutrophil functions subverted by Porphyromonas gingivalis. J Oral Microbiol. 2016; 8: 30936. doi: http://dx.doi.org/10.3402/jom.v8.30936.
  • Olsen I, Singhrao SK. Can oral infection be a risk factor for Alzheimer’s disease?. J Oral Microbiol. 2015; 7: 29143. doi: http://dx.doi.org/10.3402/jom.v7.29143.
  • Vernal R, Diaz-Guerra E, Silva A, Sanz M, Garcia-Santz JA. Distinct human T-lymphocyte responses triggered by Porphyromonas gingivalis capsular serotypes. J Clin Periodontol. 2014; 41: 19–30. doi: http://dx.doi.org/10.1111/jcpe.12176.
  • Darveau RP, Hajishengallis G, Curtis MA. Porphyromonas gingivalis as a potential community activist for disease. J Dent Res. 2012; 91: 816–20.
  • Hajishengallis G. Editorial: a toll gate to escape T cells. J Leukoc Biol. 2013; 93: 3–5. doi: http://dx.doi.org/10.1189/jlb.0912465.
  • Coats SR, Jones JW, Braham PH, Do CT, Braham PH, Bainbridge BW, etal. Human toll-like receptor 4 responses to P. gingivalis are regulated by lipid A 1- and 4’-phosphatase activities. Cell Microbiol. 2009; 11: 1587–99. doi: http://dx.doi.org/10.1111/j.1462-5822.2009.01349.x.
  • Singhrao SK, Harding A, Poole S, Kesavalu L, Crean S. Porphyromonas gingivalis periodontal infection and its putative links with Alzheimer’s disease. Mediators Inflamm. 2015; 2015: 137357. doi: http://dx.doi.org/10.1155/2015/137357.
  • Teng YT. Protective and destructive immunity in the periodonticum. Part 2 – T-cell mediated immunity in the periodontium. J Dent Res. 2006; 85: 209–19.
  • Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux NY, etal. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 2006; 169: 987–98.
  • Takeichi D, Haber J, Kawai T, Smith DJ, Moro I, Taubman MA. Cytokine profiles of T-lymphocytes from gingival tissues with pathological pocketing. J Dent Res. 2000; 79: 1548–55.
  • Vernal R, Dutzan N, Chaparro A, Puente J, Valenzuela MA, Gamonal J. Levels of interleukin-17 in gingival crevicular fluid and in supernatants of cellular cultures of gingival tissue from patients with chronic periodontitis. J Clin Periodontol. 2005; 32: 383–9. doi: http://dx.doi.org/10.1111/j.1600-051X.2005.00684.x.
  • Gemmell E, Yamazaki K, Seymour GJ. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontol 2000. 2007; 43: 14–40.
  • Gaffen SL, Hajishengallis G. A new inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res. 2008; 87: 817–28.
  • Graves DT, Oates T, Garlet GP. Review of osteoimmunology and the host response in endodontic and periodontal lesions. J Oral Microbiol. 2011; 3: 5304. doi: http://dx.doi.org/10.3402/jom.v3i0.5304.
  • Baker PJ, Dixon M, Evans RT, Dufour L, Johnson E, Roopenian DC. CD+ T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. Infect Immun. 1999; 67: 2804–9.
  • Baker PJ, Dixon M, Roopenian DC. Genetic control of susceptibility to Porphyromonas gingivalis-induced alveolar bone loss in mice. Infect Immun. 2000; 68: 5864–8.
  • Kong YY, Boyle WJ, Penninger JM. Osteoprotegerin ligand: a common link between osteoclastogenesis, lymph node formation and lymphocyte development. Immunol Cell Biol. 1999; 77: 188–93.
  • Theill LE, Boyle WJ, Penninger JM. RANKL-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol. 2002; 20: 795–823.
  • Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, etal. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999; 402: 304–9.
  • Teng YT, Nguyen H, Gao X, Kong YY, Gorczynski RM, Singh B, etal. Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest. 2000; 106: R59–67.
  • Taubman MA, Kawai T. Involvement of T lymphocytes in periodontal disease and in direct and indirect induction of bone resorption. Crit Rev Oral Biol Med. 2001; 12: 125–35.
  • Kawai T, Eisen-Lev R, Seki M, Eastcott JW, Wilson ME, Taubman MA. Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease. J Immunol. 2000; 164: 2102–9.
  • Valverde P, Kawai T, Taubman MA. Selective blockade of voltage-gated potassium channels reduces inflammatory bone resorption in experimental periodontal disease. J Bone Min Res. 2004; 19: 155–64.
  • Han X, Kawai T, Eastcott JW, Taubman MA. Bacterial-responsive B lymphocytes induce periodontal bone resorption. J Immunol. 2006; 176: 625–31.
  • Taubman MA, Ebersole JL, Smith DJ. Genco RJ, Mergenhangen SE. Association between systemic and local antibody and periodontal diseases. Host parasite interactions in periodontal diseases. 1982; Washington, DC: American Society for Microbiology. 283–98.
  • Yoshie H, Taubman MA, Olson CL, Ebersole JL, Smith DJ. Periodontal bone loss and immune characteristics after adoptive transfer of Actinobacillus-sensitized T cells to rats. J Periodontal Res. 1987; 22: 499–505.
  • Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999; 20: 345–57.
  • Valverde P, Kawai T, Taubman MA. Potasium channel-blockers as therapeutic agents to interfere with bone resorption of periodontal disease. J Dent Res. 2005; 84: 488–99.
  • Anderson KM, Olson KE, Estes KA, Flanagan K, Gendelman HE, Mosley RL. Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders. Transl Neurodegener. 2014; 3: 25. doi: http://dx.doi.org/10.1186/2047-9158-3-25.
  • Moutsopoulos NM, Kling HM, Angelov N, Jin W, Palmer RJ, Nares S, etal. P. gingivalis promotes Th17 inducing pathways in chronic periodontitis. J Autoimmun. 2012; 39: 294–303. doi: http://dx.doi.org/10.1016/j.jaut.2012.03.003.
  • Gaddis DE, Maynard CL, Weaver CT, Michalek SM, Katz J. Role of TLR2-dependent IL-10 production in the inhibition of the initial IFN-γ T cell response to Porphyromonas gingivalis. J Leukoc Biol. 2013; 93: 21–31. doi: http://dx.doi.org/10.1189/jlb.0512220.
  • Khalaf H, Bengtsson T. Altered T-cell responses by the periodontal pathogen Porphyromonas gingivalis. PLoS One. 2012; 7: e45192. doi: http://dx.doi.org/10.1371/journal.pone.0045192.
  • Zheng SG, Wang J, Wang P, Gray JD, Horwitz DA. IL-2 is essential for TGF-beta to convert naïve CD4+CD25- cells to CD25+ Fox3+ regulatory T cells and for expansion of these cells. J Immunol. 2007; 178: 2018–27.
  • Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19: 683–765.
  • Filippi CM, von Herrath MG. IL-10 and the resolution of infections. J Pathol. 2008; 214: 224–30.
  • Al-Rasheed A, Scheerens H, Rennick DM, Fletcher HM, Tatakis DN. Accelerated alveolar bone loss in mice lacking interleukin-10. J Dent Res. 2003; 82: 632–5.
  • Sasaki H, Okamatsu Y, Kawai T, Kent R, Taubman M, Stashenko P. The interleukin-10 knockout mouse is highly susceptible to Porphyromonas gingivalis-induced alveolar bone loss. J Periodontal Res. 2004; 39: 432–41.
  • Herminajeng E, Sosroseno W, Bird PS, Seymour GJ. The effects of interleukin-10 depletion in vivo on the immune response to Porphyromonas gingivalis in a murine model. J Periodontol. 2001; 72: 1527–34.
  • Kobayashi R, Kono T, Bolerjack BA, Fukuyama Y, Gilbert RS, Fujihashi M, etal. Induction of IL-10-producing CD4+ T-cells in chronic periodontitis. J Dent Res. 2011; 90: 653–8. doi: http://dx.doi.org/10.1177/0022034510397838.
  • Kitamura Y, Matono S, Aida Y, Hirofuji T, Maeda K. Gingipains in the culture supernatant of Porphyromonas gingivalis cleave CD4 and CD8 on human T cells. J Periodontal Res. 2002; 37: 464–8.
  • Gemmell E, Drysdale KE, Seymour GJ. Gene expression in splenic CD4 and CD8 cells from BALB/c mice immunized with Porphyromonas gingivalis. J Periodontol. 2006; 77: 622–33. doi: http://dx.doi.org/10.1902/jop.2006.050211.
  • Wang L, Guan N, Jin Y, Lin X, Gao H. Subcutaneous vaccination with Porphyromonas gingivalis ameliorates periodontitis by modulating Th17/Treg imbalance in a murine model. Int Immunopharmacol. 2015; 25: 65–73. doi: http://dx.doi.org/10.1016/j.intimp.2015.01.007.
  • Wang L, Wang J, Jin Y, Gao H, Lin X. Oral administration of all-trans retinoic acid suppresses experimental periodontitis by modulating the Th17/Treg imbalance. J Periodontol. 2014; 85: 740–50. doi: http://dx.doi.org/10.1902/jop.2013.130132.
  • Jauregui CE, Wang Q, Wright CJ, Takeuchi H, Uriarte SM, Lamont RJ. Suppression of T-cell chemokines by Porphyromonas gingivalis. Infect Immun. 2013; 81: 2288–95. doi: http://dx.doi.org/10.1128/IAI.00264-13.
  • Darveau RP, Belton CM, Reife RA, Lamont RJ. Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis . Infect Immun. 1998; 66: 1660–5.
  • Cole AM, Ganz T, Liese AM, Burdick MD, Liu L, Strieter RM. Cutting edge: IFN-inducible ELR- CXC chemokines display defensin-like antimicrobial activity. J Immunol. 2001; 167: 623–7.
  • Yang D, Chen Q, Hoover DM, Staley P, Tucker KD, Lubkowski J, etal. Many chemokines including CCL20/MIP-3α display antimicrobial activity. J Leukoc Biol. 2003; 74: 448–55. doi: http://dx.doi.org/10.1189/jlb.0103024.
  • Marchesan JT, Morelli T, Lundy SK, Jiao Y, Lim S, Inohara N, etal. Divergence of the systemic immune response following oral infection with distinct strains of Porphyromonas gingivalis. Mol Oral Microbiol. 2012; 27: 483–95. doi: http://dx.doi.org/10.1111/omi.12001.
  • Waller T, Kesper L, Hirschfeld J, Dommisch H, Kölpin J, Oldenburg J, etal. Porphyromonas gingivalis outer membrane vesicles induce selective TNF tolerance in a TLR4- and mTOR-dependent manner. Infect Immun. 2016; 84: 1194–204. doi: http://dx.doi.org/10.1128/IAI.01390-15.
  • Mattila KJ, Valle MJ, Nieminen MS, Valtonen VV, Hietaniemi KL. Dental infections and coronary atherosclerosis. Atherosclerosis. 1993; 103: 205–11.
  • Matilla K, Valtonen NM, Rasi V, Huttunen J. Association between dental health and acute myocardial infection. BMJ. 1989; 298: 779–82.
  • Lockhart PB, Bolger AF, Papapanou PN, Osinbowale O, Trevisan M, Levison ME, etal. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation. 2012; 125: 2520–44.
  • Tonetti MS. Periodontitis and risk for atherosclerosis: an update on intervention trials. J Clin Periodontol. 2009; 36(Suppl 10): 15–19. doi: http://dx.doi.org/10.1111/j.1600-051X.2009.01417.x.
  • Miyauchi S, Maekawa T, Aoki Y, Miyazawa H, Tabeta K, Nakajima T, etal. Oral infection with Porphyromonas gingivalis and systemic cytokine profile in C57BL/6.KOR-ApoEshl mice. J Periodontal Res. 2012; 47: 402–8. doi: http://dx.doi.org/10.1111/j.1600-0765.2011.01441.x.
  • Maekawa T, Takahashi N, Tabeta K, Aoki Y, Miyashita H, Miyauchi S, etal. Chronic oral infection with Porphyromonas gingivalis accelerates atheroma formation by shifting the lipid profile. PLoS One. 2011; 6: e20240. doi: http://dx.doi.org/10.1371/journal.pone.0020240.
  • Pussinen PJ, Alfthan G, Jousilathi P, Paju S, Tuomilehto J. Systemic exposure to Porphyromonas gingivalis predicts incident stroke. Atherosclerosis. 2007; 193: 222–8. doi: http://dx.doi.org/10.1016/j.atherosclerosis.2006.06.027.
  • Olsen I, Progulske-Fox A. Invasion of Porphyromonas gingivalis strains into vascular cells and tissue. J Oral Microbiol. 2015; 7: 28788. doi: http://dx.doi.org/10.3402/jom.v7.28788.
  • Cai Y, Kobayashi R, Hashizume-Takizawa T, Kurita-Ochiai T. Porphyromonas gingivalis infection enhances Th17 responses for development of atherosclerosis. Arch Oral Biol. 2014; 59: 1183–91. doi: http://dx.doi.org/10.1016/j.archoralbio.2014.07.012.
  • Yang J, Wu J, Liu Y, Huang J, Lu Z, Xie L, etal. Porphyromonas gingivalis infection reduces regulatory T cells in infected atherosclerotic patients. PLoS One. 2014; 9: e86599. doi: http://dx.doi.org/10.1371/journal.pone.0086599.
  • Yuan XL, Chen L, Zhang TT, Ma YH, Zhou YL, Zhao Y, etal. Gastric cancer cells induce human CD4+Foxp3+ regulatory T cells through the production of TGF-β1. World J Gastroenterol. 2011; 17: 2019–27. doi: http://dx.doi.org/10.3748/wjg.v17.i15.2019.
  • Groux H, O’Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, etal. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997; 389: 737–42.
  • Cheng X, Yu X, Ding YJ, Fu QQ, Xie JJ, Tang TT, etal. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008; 127: 89–97. doi: http://dx.doi.org/10.1016/j.clim.2008.01.009.
  • Montagne A, Pa J, Zlokovic BV. Vascular plasticity and cognition during normal aging and dementia. JAMA Neurol. 2015; 72: 495–6. doi: http://dx.doi.org/10.1001/jamaneurol.2014.4636.
  • Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, etal. Alzheimer genetic analysis group. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013; 368: 117–27. doi: http://dx.doi.org/10.1056/NEJMoa1211851.
  • Baruch K, Rosenzweig N, Kertser A, Deczkowska A, Sharif AM, Spinrad A, etal. Breaking immune tolerance by targeting Foxp3+ regulatory T cells mitigates Alzheimer’s disease pathology. Nat Commun. 2015; 6: 7967. doi: http://dx.doi.org/10.1038/ncomms8967.
  • Zenaro E, Pietronigro E, Della Bianca V, Piacentino G, Marongiu L, Budui S, etal. Neutrophils promote Alzheimer’s disease-like pathology and cognitive decline via LFA-1 integrin. Nat Med. 2015; 21: 880–6. doi: http://dx.doi.org/10.1038/nm.3913.
  • Marsh SE, Abud EM, Lakatos A, Karimzadeh A, Yeung ST, Davtyan H, etal. The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function. Proc Natl Acad Sci USA. 2016; 113: E1316–25. doi: http://dx.doi.org/10.1073/pnas.1525466113/-/DC Supplemental.
  • Singhrao SK, Harding A, Chukkapalli S, Olsen I, Kesavalu L, Crean S. Apolipoprotein E related co-morbidities and Alzheimer’s disease. J Alzheimers Dis. 2016; 51: 935–48. doi: http://dx.doi.org/10.3233/JAD150690.
  • Togo T, Akiyama H, Iseki E, Kondo H, Ikeda K, Kato M, etal. Occurrence of T cells in the brain of Alzheimer’s disease and other neurological diseases. J Neuroimmunol. 2002; 124: 83–92.
  • Poole S, Singhrao SK, Kesavalu L, Curtis MA, Crean S. Determining the presence of virulence factors in short-term postmortem Alzheimer’s disease brain tissue. J Alzheimers Dis. 2013; 36: 665–77. doi: http://dx.doi.org/10.3233/JAD-121918.
  • Baron R, Nemirovsky A, Harpaz I, Cohen H, Owens T, Monsonego A. IFN-γ enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer’s disease. FASEB J. 2008; 22: 2843–52. doi: http://dx.doi.org/10.1096/fj.08-105866.
  • Hohlfeld R. Neurotrophic cross-talk between the nervous and immune systems: relevance for repair strategies in multiple sclerosis?. J Neurol Sci. 2008; 265: 93–6. doi: http://dx.doi.org/10.1016/j.jns.2007.03.012.
  • Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol. 2007; 8: 191–7.
  • Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008; 133: 775–87.
  • Grubeck-Loebenstein B, Wick G. The aging of the immune system. Adv Immunol. 2002; 80: 243–84.
  • Plackett TP, Boehmer ED, Faunce DE, Kovacs EJ. Aging and innate immune cells. J Leukoc Biol. 2004; 76: 291–9. doi: http://dx.doi.org/10.1189/jlb.1103592.
  • Sun Y, Li H, Yang M-F, Shu W, Sun M-J, Xu Y. Effects of aging on endotoxin tolerance induced by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli. PLoS One. 2012; 7: 139224. doi: http://dx.doi.org/10.1371/journal.pone.0039224.
  • Zaric S, Shelburne C, Darveau R, Quinn DJ, Weldon S, Taggart CC, etal. Impaired immune tolerance to Porphyromonas gingivalis lipopolysaccharide promotes neutrophil migration and decreased apoptosis. Infect Immun. 2010; 78: 4151–6. doi: http://dx.doi.org/10.1128/IAI.00600-10.
  • Kajiya M, Giro G, Taubman MA, Han X, Mayer MP, Kawai T. Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease. J Oral Microbiol. 2010; 2: 5532. doi: http://dx.doi.org/10.3402/jom.v2i0.5532.
  • Han X, Kawai T, Taubman MA. Interference with immune-cell-mediated bone resorption in periodontal disease. Periodontol 2000. 2007; 45: 76–94.
  • Taubman MA, Kawai T, Han X. The new concept of periodontal disease pathogenesis requires new and novel therapeutic strategies. J Clin Periodontol. 2007; 34: 367–9.
  • Han X, Lin X, Yu X, Lin J, Kawai T, LaRosa KB, etal. Porphyromonas gingivalis infection-associated periodontal bone resorption is dependent on receptor activator of NF-κB ligand. Infect Immun. 2013; 81: 1502–9.
  • Lin X, Han X, Kawai T, Taubman MA. Antibody to receptor activator of NF-κB ligand ameliorates T cell-mediated periodontal bone resorption. Infect Immun. 2011; 79: 911–17.
  • Gaffen SL, Herzberg MC, Taubman MA, Van Dyke TE. Recent advances in host defense mechanisms/therapies against oral infectious diseases and consequences for systemic disease. Adv Dent Res. 2014; 26: 30–7. doi: http://dx.doi.org/10.1177/0022034514525778.