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Research Article

Host surface ectonucleotidase-CD73 and the opportunistic pathogen, Porphyromonas gingivalis, cross-modulation underlies a new homeostatic mechanism for chronic bacterial survival in human epithelial cells

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 414-429 | Received 22 Sep 2019, Accepted 14 Jan 2020, Published online: 18 May 2020

References

  • Yilmaz O, Jungas T, Verbeke P, et al. Activation of the phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis. Infect Immun. 2004;72:3743–3751.
  • Kolenbrander PE. American society for microbiology. Oral microbial communities: genomic inquiry and interspecies communication. Washington (DC): ASM Press; 2011.
  • Choi CH, Spooner R, DeGuzman J, et al. Porphyromonas gingivalis-nucleoside-diphosphate-kinase inhibits ATP-induced reactive-oxygen-species via P2X7 receptor/NADPH-oxidase signalling and contributes to persistence. Cell Microbiol. 2013;15:961–976.
  • Yilmaz O. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay. Microbiology. 2008;154:2897–2903.
  • Dale BA. Periodontal epithelium: a newly recognized role in health and disease. Periodontol 2000. 2002;30:70–78.
  • Burnstock G. Purinergic signalling in the gastrointestinal tract and related organs in health and disease. Purinergic Signal. 2014;10:3–50.
  • Ohman J, Erlinge D. The touching story of purinergic signaling in epithelial and endothelial cells. Purinergic Signal. 2012;8:599–608.
  • Atanasova K, Lee J, Roberts J, et al. Nucleoside-diphosphate-kinase of P. gingivalis is secreted from epithelial cells in the absence of a leader sequence through a pannexin-1 interactome. Sci Rep. 2016;6:37643.
  • Lee JS, Yilmaz O. Unfolding role of a danger molecule adenosine signaling in modulation of microbial infection and host cell response. Int J Mol Sci. 2018;19.
  • Miller CM, Boulter NR, Fuller SJ, et al. The role of the P2X(7) receptor in infectious diseases. PLoS Pathog. 2011;7:e1002212.
  • Spooner R, Yilmaz O. The role of reactive-oxygen-species in microbial persistence and inflammation. Int J Mol Sci. 2011;12:334–352.
  • Guerra AN, Gavala ML, Chung HS, et al. Nucleotide receptor signalling and the generation of reactive oxygen species. Purinergic Signal. 2007;3:39–51.
  • Yilmaz O, Lee KL. The inflammasome and danger molecule signaling: at the crossroads of inflammation and pathogen persistence in the oral cavity. Periodontol 2000. 2015;69:83–95.
  • Zimmermann H. 5ʹ-Nucleotidase: molecular structure and functional aspects. Biochem J. 1992;285(Pt 2):345–365.
  • Linden J. Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol. 2001;41:775–787.
  • Jalkanen J, Hollmen M, Jalkanen S, et al. Regulation of CD73 in the development of lower limb atherosclerosis. Purinergic Signal. 2017;13:127–134.
  • Eckle T, Fullbier L, Wehrmann M, et al. Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury. J Immunol. 2007;178:8127–8137.
  • Alam MS, Kurtz CC, Rowlett RM, et al. CD73 is expressed by human regulatory T helper cells and suppresses proinflammatory cytokine production and Helicobacter felis-induced gastritis in mice. J Infect Dis. 2009;199:494–504.
  • Gao ZW, Wang HP, Lin F, et al. CD73 promotes proliferation and migration of human cervical cancer cells independent of its enzyme activity. BMC Cancer. 2017;17:135.
  • Velasquez S, Eugenin EA. Role of Pannexin-1 hemichannels and purinergic receptors in the pathogenesis of human diseases. Front Physiol. 2014;5:96.
  • Alam MS, Kuo JL, Ernst PB, et al. Ecto-5ʹ-nucleotidase (CD73) regulates host inflammatory responses and exacerbates murine salmonellosis. Sci Rep. 2014;4:4486.
  • Francois V, Shehade H, Acolty V, et al. Intestinal immunopathology is associated with decreased CD73-generated adenosine during lethal infection. Mucosal Immunol. 2014;8:773.
  • Wang Y, Telesford KM, Ochoa-Reparaz J, et al. An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling. Nat Commun. 2014;5:4432.
  • Bou Ghanem EN. mSphere of influence: adenosine in host defense against bacterial pneumonia-friend or foe? mSphere. 2019;4. DOI:https://doi.org/10.1128/mSphere.00326-19
  • Atanasova KR, Yilmaz O. Prelude to oral microbes and chronic diseases: past, present and future. Microbes Infect. 2015;17:473–483.
  • Aas JA, Paster BJ, Stokes LN, et al. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol. 2005;43:5721–5732.
  • Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol. 2012;10:717–725.
  • Spooner R, Weigel KM, Harrison PL, et al. In situ anabolic activity of periodontal pathogens Porphyromonas gingivalis and Filifactor alocis in chronic periodontitis. Sci Rep. 2016;6:33638.
  • Olsen I, Yilmaz O. Possible role of Porphyromonas gingivalis in orodigestive cancers. J Oral Microbiol. 2019;11:1563410.
  • Atanasova KR, Yilmaz O. Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association. Mol Oral Microbiol. 2014;29:55–66.
  • Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5:eaau3333.
  • Lee K, Roberts JS, Choi CH, et al. Porphyromonas gingivalis traffics into endoplasmic reticulum-rich-autophagosomes for successful survival in human gingival epithelial cells. Virulence. 2018;9:845–859.
  • Colombo AV, Silva CM, Haffajee A, et al. Identification of oral bacteria associated with crevicular epithelial cells from chronic periodontitis lesions. J Med Microbiol. 2006;55:609–615.
  • Dzink JL, Gibbons RJ, Childs WC 3rd, et al. The predominant cultivable microbiota of crevicular epithelial cells. Oral Microbiol Immunol. 1989;4:1–5.
  • Yilmaz O, Verbeke P, Lamont RJ, et al. Intercellular spreading of Porphyromonas gingivalis infection in primary gingival epithelial cells. Infect Immun. 2006;74:703–710.
  • Dorn BR, Dunn WA Jr., Progulske-Fox A. Bacterial interactions with the autophagic pathway. Cell Microbiol. 2002;4:1–10.
  • Yilmaz O, Yao L, Maeda K, et al. ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis. Cell Microbiol. 2008;10:863–875.
  • Hajishengallis G. Immune evasion strategies of Porphyromonas gingivalis. J Oral Biosci. 2011;53:233–240.
  • Roberts JS, Atanasova KR, Lee J, et al. Opportunistic pathogen Porphyromonas gingivalis modulates danger signal ATP-mediated antibacterial NOX2 pathways in primary epithelial cells. Front Cell Infect Microbiol. 2017;7:291.
  • Hung SC, Choi CH, Said-Sadier N, et al. P2X4 assembles with P2X7 and pannexin-1 in gingival epithelial cells and modulates ATP-induced reactive oxygen species production and inflammasome activation. PloS One. 2013;8:e70210.
  • Yilmaz O, Sater AA, Yao L, et al. ATP-dependent activation of an inflammasome in primary gingival epithelial cells infected by Porphyromonas gingivalis. Cell Microbiol. 2010;12:188–198.
  • Johnson L, Atanasova KR, Bui PQ, et al. Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase. Microbes Infect. 2015;17:369–377.
  • Lee J, Roberts JS, Atanasova KR, et al. A novel kinase function of a nucleoside-diphosphate-kinase homologue in Porphyromonas gingivalis is critical in subversion of host cell apoptosis by targeting heat-shock protein 27. Cell Microbiol. 2018;20:e12825.
  • Mao S, Park Y, Hasegawa Y, et al. Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis. Cell Microbiol. 2007;9:1997–2007.
  • Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16:745–759.
  • Jahngen EG, Brecx M, Rossomando EF. High-performance liquid chromatography analysis of purine nucleosides in human gingival crevicular fluid. Arch Oral Biol. 1984;29:607–610.
  • Barnes VM, Teles R, Trivedi HM, et al. Acceleration of purine degradation by periodontal diseases. J Dent Res. 2009;88:851–855.
  • Gordon JL. Extracellular ATP: effects, sources and fate. Biochem J. 1986;233:309–319.
  • Haskó G, Linden J, Cronstein B, et al. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 2008;7:759–770.
  • Murakami S, Hashikawa T, Saho T, et al. Adenosine regulates the IL-1 beta-induced cellular functions of human gingival fibroblasts. Int Immunol. 2001;13:1533–1540.
  • Hashikawa T, Takedachi M, Terakura M, et al. Involvement of CD73 (ecto-5ʹ-nucleotidase) in adenosine generation by human gingival fibroblasts. J Dent Res. 2003;82:888–892.
  • Bitto A, Oteri G, Pisano M, et al. Adenosine receptor stimulation by polynucleotides (PDRN) reduces inflammation in experimental periodontitis. J Clin Periodontol. 2013;40:26–32.
  • Sun CX, Wall NR, Angelov N, et al. Changes in mRNA expression of adenosine receptors in human chronic periodontitis. Chin J Dent Res. 2011;14:113–120.
  • Spooner R, DeGuzman J, Lee KL, et al. Danger signal adenosine via adenosine 2a receptor stimulates growth of Porphyromonas gingivalis in primary gingival epithelial cells. Mol Oral Microbiol. 2014;29:67–78.
  • Sandros J, Karlsson C, Lappin DF, et al. Cytokine responses of oral epithelial cells to Porphyromonas gingivalis infection. J Dent Res. 2000;79:1808–1814.
  • Sugawara S, Uehara A, Tamai R, et al. Innate immune responses in oral mucosa. J Endotoxin Res. 2002;8:465–468.
  • Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol. 2008;8:411–420.
  • Knapp K, Zebisch M, Pippel J, et al. Crystal structure of the human ecto-5ʹ-nucleotidase (CD73): insights into the regulation of purinergic signaling. Structure. 2012;20:2161–2173.
  • Rahimova R, Fontanel S, Lionne C, et al. Identification of allosteric inhibitors of the ecto-5ʹ-nucleotidase (CD73) targeting the dimer interface. PLoS Comput Biol. 2018;14:e1005943.
  • Freundlieb M, Zimmermann H, Muller CE. A new, sensitive ecto-5ʹ-nucleotidase assay for compound screening. Anal Biochem. 2014;446:53–58.
  • Iqbal J, Jirovsky D, Lee SY, et al. Capillary electrophoresis-based nanoscale assays for monitoring ecto-5ʹ-nucleotidase activity and inhibition in preparations of recombinant enzyme and melanoma cell membranes. Anal Biochem. 2008;373:129–140.
  • Lee J, Roberts JS, Atanasova KR, et al. Human primary epithelial cells acquire an epithelial-mesenchymal-transition phenotype during long-term infection by the oral opportunistic pathogen, Porphyromonas gingivalis. Front Cell Infect Microbiol. 2017;7:493.
  • Jian R, Sun Y, Wang Y, et al. CD73 protects kidney from ischemia-reperfusion injury through reduction of free radicals. APMIS. 2012;120:130–138.
  • Chisci E, De Giorgi M, Zanfrini E, et al. Simultaneous overexpression of human E5NT and ENTPD1 protects porcine endothelial cells against H2O2-induced oxidative stress and cytotoxicity in vitro. Free Radic Biol Med. 2017;108:320–333.
  • Liu J, Liu Y, Chen J, et al. The ROS-mediated activation of IL-6/STAT3 signaling pathway is involved in the 27-hydroxycholesterol-induced cellular senescence in nerve cells. Toxicol In Vitro. 2017;45:10–18.
  • Kosmidou I, Vassilakopoulos T, Xagorari A, et al. Production of interleukin-6 by skeletal myotubes: role of reactive oxygen species. Am J Respir Cell Mol Biol. 2002;26:587–593.
  • Yao L, Jermanus C, Barbetta B, et al. Porphyromonas gingivalis infection sequesters pro-apoptotic bad through Akt in primary gingival epithelial cells. Mol Oral Microbiol. 2010;25:89–101.
  • Sitkovsky MV, Ohta A. The ‘danger’ sensors that STOP the immune response: the A2 adenosine receptors? Trends Immunol. 2005;26:299–304.
  • Bours MJ, Swennen EL, Di Virgilio F, et al. Adenosine 5ʹ-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther. 2006;112:358–404.
  • Ishii KJ, Akira S. Potential link between the immune system and metabolism of nucleic acids. Curr Opin Immunol. 2008;20:524–529.
  • Cekic C, Linden J. Purinergic regulation of the immune system. Nat Rev Immunol. 2016;16:177–192.
  • Allard D, Allard B, Gaudreau PO, et al. CD73-adenosine: a next-generation target in immuno-oncology. Immunotherapy. 2016;8:145–163.
  • Ohta A, Sitkovsky M. Extracellular adenosine-mediated modulation of regulatory T cells. Front Immunol. 2014;5:304.
  • Bou Ghanem EN, Clark S, Roggensack SE, et al. Extracellular Adenosine Protects against Streptococcus pneumoniae Lung Infection by Regulating Pulmonary Neutrophil Recruitment. PLoS Pathog. 2015;11:e1005126.
  • Kao DJ, Saeedi BJ, Kitzenberg D, et al. Intestinal epithelial ecto-5ʹ-nucleotidase (CD73) regulates intestinal colonization and infection by nontyphoidal salmonella. Infect Immun. 2017;85.
  • Alam MS, Kurtz CC, Wilson JM, et al. A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence. Mucosal Immunol. 2009;2:232–242.
  • Petit-Jentreau L, Jouvion G, Charles P, et al. Ecto-5ʹ-nucleotidase (CD73) deficiency in Mycobacterium tuberculosis-infected mice enhances neutrophil recruitment. Infect Immun. 2015;83:3666–3674.
  • Costales MG, Alam MS, Cavanaugh C, et al. Extracellular adenosine produced by ecto-5ʹ-nucleotidase (CD73) regulates macrophage pro-inflammatory responses, nitric oxide production, and favors Salmonella persistence. Nitric Oxide. 2018;72:7–15.
  • Traut TW. Physiological concentrations of purines and pyrimidines. Mol Cell Biochem. 1994;140:1–22.
  • Takashiba S, Naruishi K, Murayama Y. Perspective of cytokine regulation for periodontal treatment: fibroblast biology. J Periodontol. 2003;74:103–110.
  • Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer. 2005;41:2502–2512.
  • Dutzan N, Kajikawa T, Abusleme L, et al. A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018;10.
  • Yost S, Duran-Pinedo AE, Krishnan K, et al. Potassium is a key signal in host-microbiome dysbiosis in periodontitis. PLoS Pathog. 2017;13:e1006457.
  • Meduri GU, Kanangat S, Stefan J, et al. Cytokines IL-1beta, IL-6, and TNF-alpha enhance in vitro growth of bacteria. Am J Respir Crit Care Med. 1999;160:961–967.
  • Porat R, Clark BD, Wolff SM, et al. Enhancement of growth of virulent strains of Escherichia coli by interleukin-1. Science. 1991;254:430–432.
  • Denis M, Gregg EO. Recombinant tumour necrosis factor-alpha decreases whereas recombinant interleukin-6 increases growth of a virulent strain of Mycobacterium avium in human macrophages. Immunology. 1990;71:139–141.
  • Baran P, Hansen S, Waetzig GH, et al. The balance of interleukin (IL)-6, IL-6.soluble IL-6 receptor (sIL-6R), and IL-6.sIL-6R.sgp130 complexes allows simultaneous classic and trans-signaling. J Biol Chem. 2018;293:6762–6775.
  • Saito A, Kokubu E, Inagaki S, et al. Porphyromonas gingivalis entry into gingival epithelial cells modulated by Fusobacterium nucleatum is dependent on lipid rafts. Microb Pathog. 2012;53:234–242.
  • Lamont RJ, Chan A, Belton CM, et al. Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun. 1995;63:3878–3885.
  • Belton CM, Izutsu KT, Goodwin PC, et al. Fluorescence image analysis of the association between Porphyromonas gingivalis and gingival epithelial cells. Cell Microbiol. 1999;1:215–223.
  • Baker PJ, Dixon M, Evans RT, et al. Heterogeneity of Porphyromonas gingivalis strains in the induction of alveolar bone loss in mice. Oral Microbiol Immunol. 2000;15:27–32.
  • Oda D, Watson E. Human oral epithelial cell culture I. Improved conditions for reproducible culture in serum-free medium. In Vitro Cell Dev Biol. 1990;26:589–595.
  • Yilmaz O, Watanabe K, Lamont RJ. Involvement of integrins in fimbriae-mediated binding and invasion by Porphyromonas gingivalis. Cell Microbiol. 2002;4:305–314.
  • Garcia-Hernandez MH, Portales-Cervantes L, Cortez-Espinosa N, et al. Expression and function of P2X(7) receptor and CD39/Entpd1 in patients with type 2 diabetes and their association with biochemical parameters. Cell Immunol. 2011;269:135–143.
  • Xu S, Shao QQ, Sun JT, et al. Synergy between the ectoenzymes CD39 and CD73 contributes to adenosinergic immunosuppression in human malignant gliomas. Neuro Oncol. 2013;15:1160–1172.
  • Adzic M, Nedeljkovic N. Unveiling the role of Ecto-5ʹ-nucleotidase/CD73 in astrocyte migration by using pharmacological tools. Front Pharmacol. 2018;9:153.
  • Nhu QM, Shirey K, Teijaro JR, et al. Novel signaling interactions between proteinase-activated receptor 2 and Toll-like receptors in vitro and in vivo. Mucosal Immunol. 2010;3:29–39.
  • Tran SD, Rudney JD. Multiplex PCR using conserved and species-specific 16S rRNA gene primers for simultaneous detection of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. J Clin Microbiol. 1996;34:2674–2678.
  • Lyons SR, Griffen AL, Leys EJ. Quantitative real-time PCR for Porphyromonas gingivalis and total bacteria. J Clin Microbiol. 2000;38:2362–2365.