Skip to main content Skip to main navigation menu Skip to site footer

The role of the immune response in the development of pneumonia arising from oral periodontitis: a literature review


Link of Video Abstract:


A growing evidence links periodontitis, a chronic inflammatory disease of the oral cavity, to the development of systemic inflammation. One of the most commonly reported is pneumonia, arising from aspiration of the periodontal pathogens into the lung tissue. In high-risk individuals, the morbidity and mortality rate is high, raising the concern for prevention measures. Secondary systemic effects are proposed to arise from both direct periodontal pathogens spread and through leakage of bacterial byproducts and local inflammatory cytokines to the bloodstream. The association of periodontitis and systemic diseases is bi-directional, as systemic diseases may, in turn, increase the incidence and severity of periodontal diseases. Here, the conflicting roles of the immune system in both limiting pathogen growth and its potential catastrophic inflammatory activation is further discussed. In addition, possible approaches to prevent periodontitis from spreading into the respiratory organs are also proposed. Given the large number of the population affected by periodontitis, a comprehensive understanding of the pathomechanisms of the development of systemic diseases, notably pneumonia, as well as the discovery of prevention and therapeutic approaches, is urgently needed.


  1. El Attar MM, Zaghloup MZ, Elmenoufr HS. Role of periodontitis in hospital-acquired pneumonia. East Mediterr Health J. 2010;16(5):563-9.
  2. Gomes-Filho IS, de Oliveira TF, da Cruz SS, Passos-Soares Jde S, Trindade SC, Oliveira MT, et al. Influence of periodontitis in the development of nosocomial pneumonia: a case control study. J Periodontol. 2014;85(5):e82-90.
  3. Jeronimo LS, Abreu LG, Cunha FA, Esteves Lima RP. Association between periodontitis and nosocomial pneumonia: a systematic review and meta-analysis of observational studies. Oral Health Prev Dent. 2020;18(1):11-7.
  4. Kim SJ, Kim K, Choi S, Chang J, Kim SM, Park SM, et al. Chronic periodontitis and community-acquired pneumonia: a population-based cohort study. BMC Pulm Med. 2019;19(1):268.
  5. Kononen E, Gursoy M, Gursoy UK. Periodontitis: a multifaceted disease of tooth-supporting tissues. J Clin Med. 2019;8(8).
  6. O'Dwyer MC, Furgal A, Furst W, Ramakrishnan M, Capizzano N, Sen A, et al. The prevalence of periodontitis among US adults with multimorbidity using NHANES data 2011-2014. J Am Board Fam Med. 2023;36(2):313-24.
  7. Holmstrup P, Glick M. Treatment of periodontal disease in the immunodeficient patient. Periodontol 2000. 2002;28:190-205.
  8. Arigbede AO, Babatope BO, Bamidele MK. Periodontitis and systemic diseases: A literature review. J Indian Soc Periodontol. 2012;16(4):487-91.
  9. Scannapieco FA, Ho AW. Potential associations between chronic respiratory disease and periodontal disease: analysis of National Health and Nutrition Examination Survey III. J Periodontol. 2001;72(1):50-6.
  10. de Melo Neto JP, Melo MS, dos Santos-Pereira SA, Martinez EF, Okajima LS, Saba-Chujfi E. Periodontal infections and community-acquired pneumonia: a case-control study. Eur J Clin Microbiol Infect Dis. 2013;32(1):27-32.
  11. Awano S, Ansai T, Takata Y, Soh I, Akifusa S, Hamasaki T, et al. Oral health and mortality risk from pneumonia in the elderly. J Dent Res. 2008;87(4):334-9.
  12. Brock M, Bahammam S, Sima C. The relationships among periodontitis, pneumonia and COVID-19. Front Oral Health. 2021;2:801815.
  13. Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, Naqvi A, et al. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog. 2010;6(1):e1000713.
  14. Pride DT, Salzman J, Haynes M, Rohwer F, Davis-Long C, White RA, et al. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J. 2012;6(5):915-26.
  15. Armitage GC. Periodontal diagnoses and classification of periodontal diseases. Periodontol 2000. 2004;34:9-21.
  16. Martin R, Miquel S, Ulmer J, Kechaou N, Langella P, Bermudez-Humaran LG. Role of commensal and probiotic bacteria in human health: a focus on inflammatory bowel disease. Microb Cell Fact. 2013;12:71.
  17. Baty JJ, Stoner SN, Scoffield JA. Oral commensal Streptococci: gatekeepers of the oral cavity. J Bacteriol. 2022;204(11):e0025722.
  18. He X, Tian Y, Guo L, Ano T, Lux R, Zusman DR, et al. In vitro communities derived from oral and gut microbial floras inhibit the growth of bacteria of foreign origins. Microb Ecol. 2010;60(3):665-76.
  19. He X, Tian Y, Guo L, Lux R, Zusman DR, Shi W. Oral-derived bacterial flora defends its domain by recognizing and killing intruders--a molecular analysis using Escherichia coli as a model intestinal bacterium. Microb Ecol. 2010;60(3):655-64.
  20. Cosseau C, Devine DA, Dullaghan E, Gardy JL, Chikatamarla A, Gellatly S, et al. The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis. Infect Immun. 2008;76(9):4163-75.
  21. MacDonald KW, Chanyi RM, Macklaim JM, Cadieux PA, Reid G, Burton JP. Streptococcus salivarius inhibits immune activation by periodontal disease pathogens. BMC Oral Health. 2021;21(1):245.
  22. Tang YL, Sim TS, Tan KS. Oral streptococci subvert the host innate immune response through hydrogen peroxide. Sci Rep. 2022;12(1):656.
  23. Ebersole JL. Humoral immune responses in gingival crevice fluid: local and systemic implications. Periodontol 2000. 2003;31:135-66.
  24. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976;34(3):235-49.
  25. Ebersole JL, Dawson DR, Morford LA, Peyyala R, Miller CS, Gonzalez OA. Periodontal disease immunology: 'double indemnity' in protecting the host. Periodontol 2000. 2013;62(1):163-202.
  26. Koshy B, Rees JS, Farnell D, Wei XQ, Waddington RJ. Array analysis for T-cell associated cytokines in gingival crevicular fluid: Identifying altered profiles associated with periodontal disease status. J Dent. 2019;85:39-46.
  27. Salvi GE, Beck JD, Offenbacher S. PGE2, IL-1 beta, and TNF-alpha responses in diabetics as modifiers of periodontal disease expression. Ann Periodontol. 1998;3(1):40-50.
  28. Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000;71(10):1554-60.
  29. Ohki T, Itabashi Y, Kohno T, Yoshizawa A, Nishikubo S, Watanabe S, et al. Detection of periodontal bacteria in thrombi of patients with acute myocardial infarction by polymerase chain reaction. Am Heart J. 2012;163(2):164-7.
  30. Dhotre S, Jahagirdar V, Suryawanshi N, Davane M, Patil R, Nagoba B. Assessment of periodontitis and its role in viridans streptococcal bacteremia and infective endocarditis. Indian Heart J. 2018;70(2):225-32.
  31. Larvin H, Kang J, Aggarwal VR, Pavitt S, Wu J. Risk of incident cardiovascular disease in people with periodontal disease: A systematic review and meta-analysis. Clin Exp Dent Res. 2021;7(1):109-22.
  32. Leng Y, Hu Q, Ling Q, Yao X, Liu M, Chen J, et al. Periodontal disease is associated with the risk of cardiovascular disease independent of sex: A meta-analysis. Front Cardiovasc Med. 2023;10:1114927.
  33. Yamanaka F, Tsujita K, Saito S. Periodontal disease as a potential risk factor of cardiovascular disease. Circ J. 2022;86(5):819-20.
  34. Dietrich T, Jimenez M, Krall Kaye EA, Vokonas PS, Garcia RI. Age-dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease. Circulation. 2008;117(13):1668-74.
  35. Skipina TM, Elhawary MM, Soliman EZ. Periodontal disease is associated with elevated atherosclerotic cardiovascular disease risk score. Am J Med Sci. 2022;364(3):327-32.
  36. Carinci F, Martinelli M, Contaldo M, Santoro R, Pezzetti F, Lauritano D, et al. Focus on periodontal disease and development of endocarditis. J Biol Regul Homeost Agents. 2018;32(2 Suppl. 1):143-7.
  37. Mojon P. Oral health and respiratory infection. J Can Dent Assoc. 2002;68(6):340-5.
  38. Bansal M, Khatri M, Taneja V. Potential role of periodontal infection in respiratory diseases - a review. J Med Life. 2013;6(3):244-8.
  39. Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review. Ann Periodontol. 2003;8(1):54-69.
  40. Bui FQ, Almeida-da-Silva CLC, Huynh B, Trinh A, Liu J, Woodward J, et al. Association between periodontal pathogens and systemic disease. Biomed J. 2019;42(1):27-35.
  41. Benedyk M, Mydel PM, Delaleu N, Plaza K, Gawron K, Milewska A, et al. Gingipains: critical factors in the development of aspiration pneumonia caused by Porphyromonas gingivalis. J Innate Immun. 2016;8(2):185-98.
  42. Imai K, Iinuma T, Sato S. Relationship between the oral cavity and respiratory diseases: Aspiration of oral bacteria possibly contributes to the progression of lower airway inflammation. Jpn Dent Sci Rev. 2021;57:224-30.
  43. Koike R, Cueno ME, Nodomi K, Tamura M, Kamio N, Tanaka H, et al. Heat-killed Fusobacterium nucleatum triggers varying heme-related inflammatory and stress responses depending on primary human respiratory epithelial cell type. Molecules. 2020;25(17):3839.
  44. Watanabe N, Yokoe S, Ogata Y, Sato S, Imai K. Exposure to Porphyromonas gingivalis induces production of proinflammatory cytokine via TLR2 from human respiratory epithelial cells. J Clin Med. 2020;9(11):3433.
  45. Hayata M, Watanabe N, Tamura M, Kamio N, Tanaka H, Nodomi K, et al. The periodontopathic Bacterium Fusobacterium nucleatum induced proinflammatory cytokine production by human respiratory epithelial cell lines and in the lower respiratory organs in mice. Cell Physiol Biochem. 2019;53(1):49-61.
  46. Hama K, Iwasa Y, Ohara Y, Iwasaki M, Ito K, Nakajima J, et al. Pneumonia incidence and oral health management by dental hygienists in long-term care facilities: A 1-year prospective multicentre cohort study. Gerodontology. 2022;39(4):374-83.
  47. Prasad R, Daly B, Manley G. The impact of 0.2% chlorhexidine gel on oral health and the incidence of pneumonia amongst adults with profound complex neurodisability. Spec Care Dentist. 2019;39(5):524-32.
  48. Son M, Jo S, Lee JS, Lee DH. Association between oral health and incidence of pneumonia: a population-based cohort study from Korea. Sci Rep. 2020;10(1):9576.
  49. van der Maarel-Wierink CD, Vanobbergen JN, Bronkhorst EM, Schols JM, de Baat C. Oral health care and aspiration pneumonia in frail older people: a systematic literature review. Gerodontology. 2013;30(1):3-9.
  50. Shen TC, Chang PY, Lin CL, Chen CH, Tu CY, Hsia TC, et al. Periodontal treatment reduces risk of adverse respiratory events in patients with chronic obstructive pulmonary disease: A propensity-matched cohort study. Medicine (Baltimore). 2016;95(20):e3735.
  51. Yang LC, Suen YJ, Wang YH, Lin TC, Yu HC, Chang YC. The association of periodontal treatment and decreased pneumonia: A nationwide population-based cohort study. Int J Environ Res Public Health. 2020;17(1):356.
  52. Silva H. Tobacco use and periodontal disease-the role of microvascular dysfunction. Biology (Basel). 2021;10(5):441.
  53. Jiang Y, Zhou X, Cheng L, Li M. The impact of smoking on subgingival microflora: from periodontal health to disease. Front Microbiol. 2020;11:66.
  54. Herryawan H, Sabirin IPR. The effectiveness of red betel leaf (Piper crocatum) extract against periodontal pathogens. Bali Med J. 2018;7(3).
  55. Araujo FG, Slifer TL, Remington JS. Effect of moxifloxacin on secretion of cytokines by human monocytes stimulated with lipopolysaccharide. Clin Microbiol Infect. 2002;8(1):26-30.
  56. Ardila CM, Fernandez N, Guzman IC. Antimicrobial susceptibility of moxifloxacin against gram-negative enteric rods from colombian patients with chronic periodontitis. J Periodontol. 2010;81(2):292-9.
  57. Ardila CM, Martelo-Cadavid JF, Boderth-Acosta G, Ariza-Garces AA, Guzman IC. Adjunctive moxifloxacin in the treatment of generalized aggressive periodontitis patients: clinical and microbiological results of a randomized, triple-blind and placebo-controlled clinical trial. J Clin Periodontol. 2015;42(2):160-8.
  58. Susanti W, Purwanto B, Cilmiaty R, Prayitno A. Investigation of Astaxanthin effect on the formation of collagen fibers for periodontal tissue repair in bacteria infected periodontitis. Bali Med J. 2020;9(2):493-5.
  59. Maekawa T, Tamura H, Domon H, Hiyoshi T, Isono T, Yonezawa D, et al. Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1. JCI Insight. 2020;5(15).

How to Cite

Hutomo, S. ., & Denise Utami Putri. (2023). The role of the immune response in the development of pneumonia arising from oral periodontitis: a literature review. Bali Medical Journal, 12(3), 2527–2531.




Search Panel