Display options
Share it on

Pathogens. 2021 May 30;10(6). doi: 10.3390/pathogens10060675.

Bacterial Cyclic Dinucleotides and the cGAS-cGAMP-STING Pathway: A Role in Periodontitis?.

Pathogens (Basel, Switzerland)

Samira Elmanfi, Mustafa Yilmaz, Wilson W S Ong, Kofi S Yeboah, Herman O Sintim, Mervi Gürsoy, Eija Könönen, Ulvi K Gürsoy

Affiliations

  1. Department of Periodontology, Institute of Dentistry, University of Turku, 20520 Turku, Finland.
  2. Department of Periodontology, Faculty of Dentistry, Biruni University, 34010 Istanbul, Turkey.
  3. Department of Chemistry and Purdue Institute for Drug Discovery and Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, Indiana, IN 47907, USA.
  4. Oral Health Care, Welfare Division, City of Turku, 20520 Turku, Finland.

PMID: 34070809 PMCID: PMC8226932 DOI: 10.3390/pathogens10060675

Abstract

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides-including c-di-GMP, c-di-AMP, and cGAMP-of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms "STING", "TBK 1", "IRF3", and "cGAS"-alone, or together with "periodontitis". Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

Keywords: STING; bacterial recognition; cyclic dinucleotides; nucleic acid; periodontitis

References

  1. Exp Mol Med. 2019 Dec 11;51(12):1-10 - PubMed
  2. J Virol. 2014 May;88(10):5328-41 - PubMed
  3. J Clin Med. 2019 Jul 31;8(8): - PubMed
  4. J Periodontol. 2013 Oct;84(10):e48-57 - PubMed
  5. EMBO J. 2014 Dec 17;33(24):2937-46 - PubMed
  6. Nat Rev Immunol. 2011 Jul 25;11(8):519-31 - PubMed
  7. Clin Implant Dent Relat Res. 2018 Aug;20(4):574-582 - PubMed
  8. Oral Dis. 2017 Mar;23(2):168-180 - PubMed
  9. J Mol Med (Berl). 2016 Oct;94(10):1085-1093 - PubMed
  10. Cell Rep. 2015 May 19;11(7):1018-30 - PubMed
  11. J Oral Microbiol. 2018 Nov 27;11(1):1538927 - PubMed
  12. J Periodontal Res. 2011 Apr;46(2):184-92 - PubMed
  13. PLoS Pathog. 2015 Dec 08;11(12):e1005324 - PubMed
  14. Front Immunol. 2012 May 16;3:118 - PubMed
  15. J Med Chem. 2020 Apr 23;63(8):3785-3816 - PubMed
  16. Arch Oral Biol. 2015 Jun;60(6):948-58 - PubMed
  17. Oral Dis. 2014 Mar;20(2):119-26 - PubMed
  18. J Periodontal Res. 2012 Feb;47(1):62-73 - PubMed
  19. Cell. 2013 Aug 29;154(5):962-970 - PubMed
  20. Nat Commun. 2016 Jun 21;7:11932 - PubMed
  21. Nature. 2013 Jun 20;498(7454):332-7 - PubMed
  22. J Leukoc Biol. 2008 Jul;84(1):311-8 - PubMed
  23. Nat Rev Immunol. 2016 Sep;16(9):566-80 - PubMed
  24. Cell Mol Immunol. 2019 Mar;16(3):236-241 - PubMed
  25. Medchemcomm. 2019 Aug 15;10(12):1999-2023 - PubMed
  26. Annu Rev Microbiol. 2018 Sep 08;72:447-478 - PubMed
  27. Nat Microbiol. 2020 Dec;5(12):1608-1615 - PubMed
  28. Nature. 2020 Oct;586(7829):429-433 - PubMed
  29. PLoS One. 2010 Mar 26;5(3):e9896 - PubMed
  30. Science. 2020 Aug 21;369(6506):993-999 - PubMed
  31. Nature. 2018 Dec;564(7736):439-443 - PubMed
  32. Immunity. 2013 May 23;38(5):870-80 - PubMed
  33. J Clin Periodontol. 2013 Apr;40 Suppl 14:S1-7 - PubMed
  34. Cell. 2005 Sep 9;122(5):669-82 - PubMed
  35. J Immunol. 2015 Oct 15;195(8):3507-12 - PubMed
  36. Cell Rep. 2020 Oct 20;33(3):108297 - PubMed
  37. FASEB J. 2020 Oct;34(10):13156-13170 - PubMed
  38. Nature. 2017 Sep 21;549(7672):394-398 - PubMed
  39. Nat Rev Immunol. 2015 Dec;15(12):760-70 - PubMed
  40. Eur J Immunol. 2004 May;34(5):1451-60 - PubMed
  41. Annu Rev Immunol. 2011;29:185-214 - PubMed
  42. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7768-E7775 - PubMed
  43. Cancer Discov. 2020 Jan;10(1):26-39 - PubMed
  44. Trends Microbiol. 2017 Nov;25(11):906-918 - PubMed
  45. Nat Immunol. 2013 Jan;14(1):19-26 - PubMed
  46. Cell. 2013 May 23;153(5):1094-107 - PubMed
  47. Nat Immunol. 2006 Feb;7(2):156-64 - PubMed
  48. Eur J Immunol. 2001 Oct;31(10):3026-37 - PubMed
  49. Nat Rev Genet. 2019 Nov;20(11):657-674 - PubMed
  50. J Clin Periodontol. 2011 Mar;38 Suppl 11:85-105 - PubMed
  51. Proteomics Clin Appl. 2020 May;14(3):e1900109 - PubMed
  52. Arthritis Rheumatol. 2016 Apr;68(4):795-804 - PubMed
  53. Cell Rep. 2018 Dec 18;25(12):3405-3421.e7 - PubMed
  54. Chem Soc Rev. 2013 Jan 7;42(1):305-41 - PubMed
  55. Nature. 2009 Oct 8;461(7265):788-92 - PubMed
  56. Curr Opin Cell Biol. 2020 Apr;63:49-56 - PubMed
  57. Cell Rep. 2013 May 30;3(5):1362-8 - PubMed
  58. Chem Commun (Camb). 2016 Aug 4;52(60):9327-42 - PubMed
  59. J Immunol. 2013 Apr 15;190(8):4349-59 - PubMed
  60. Mol Cell. 2013 Jul 25;51(2):135-9 - PubMed
  61. Front Cell Infect Microbiol. 2017 Jun 21;7:273 - PubMed
  62. Nature. 1995 May 11;375(6527):151-5 - PubMed
  63. Pathogens. 2020 Sep 26;9(10): - PubMed
  64. Cancer Cell. 2018 May 14;33(5):862-873.e5 - PubMed
  65. Science. 2018 Aug 17;361(6403):704-709 - PubMed
  66. Science. 2020 Aug 21;369(6506): - PubMed
  67. J Clin Periodontol. 2012 Mar;39(3):239-48 - PubMed
  68. Nat Immunol. 2009 Oct;10(10):1065-72 - PubMed
  69. Future Sci OA. 2016 Jan 29;2(1):FSO93 - PubMed
  70. Molecules. 2019 Nov 19;24(22): - PubMed
  71. Mol Cell. 2013 Jul 25;51(2):226-35 - PubMed
  72. Nature. 2018 Jul;559(7713):269-273 - PubMed
  73. Cell Immunol. 2011;270(1):88-93 - PubMed
  74. J Oral Sci. 2011 Sep;53(3):263-71 - PubMed
  75. PLoS One. 2020 Sep 10;15(9):e0237743 - PubMed
  76. Nature. 2008 Oct 2;455(7213):674-8 - PubMed
  77. Adv Dent Res. 2014 May;26(1):23-9 - PubMed
  78. Nat Rev Immunol. 2011 Mar;11(3):187-200 - PubMed
  79. J Immunol. 2007 Feb 15;178(4):2380-6 - PubMed

Publication Types

Grant support