Skip to main content
Top
Published in: BMC Oral Health 1/2020

Open Access 01-12-2020 | Bleeding on Probing | Research article

Differential immune cell infiltrations between healthy periodontal and chronic periodontitis tissues

Authors: Wei Li, Zheng Zhang, Zuo-min Wang

Published in: BMC Oral Health | Issue 1/2020

Login to get access

Abstract

Background

Host immunity plays an important role against oral microorganisms in periodontitis.

Methods

This study assessed the infiltrating immune cell subtypes in 133 healthy periodontal and 210 chronic periodontitis tissues from Gene Expression Omnibus (GEO) datasets using the CIBERSORT gene signature files.

Results

Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues, when compared to those in healthy controls. In contrast, memory B cells, resting dendritic, mast cells and CD4 memory cells, as well as activated mast cells, M1 and M2 macrophages, and follicular helper T cells, were mainly present in healthy periodontal tissues. Furthermore, these periodontitis tissues generally contained a higher proportion of activated CD4 memory T cells, while the other subtypes of T cells, including resting CD4 memory T cells, CD8 T cells, follicular helper T cells (TFH) and regulatory T cells (Tregs), were relatively lower in periodontitis tissues, when compared to healthy tissues. The ratio of dendritic and mast cells and macrophages was lower in periodontitis tissues, when compared to healthy tissues. In addition, there was a significant negative association of plasma cells with most of the other immune cells, such as plasma cells vs. memory B cells (γ = − 0.84), plasma cells vs. resting dendritic cells (γ = − 0.64), plasma cells vs. resting CD4 memory T cells (γ = 0.50), plasma cells versus activated dendritic cells (γ = − 0.46), plasma cells versus TFH (γ = − 0.46), plasma cells versus macrophage M2 cells (γ = − 0.43), or plasma cells versus macrophage M1 cells (γ = − 0.40), between healthy control and periodontitis tissues.

Conclusion

Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues. The infiltration of different immune cell subtypes in the periodontitis site could lead the host immunity against periodontitis.
Literature
1.
go back to reference Savage A, Eaton KA, Moles DR, Needleman I. A systematic review of definitions of periodontitis and methods that have been used to identify this disease. J Clin Periodontol. 2009;36(6):458–67. CrossRefPubMed Savage A, Eaton KA, Moles DR, Needleman I. A systematic review of definitions of periodontitis and methods that have been used to identify this disease. J Clin Periodontol. 2009;36(6):458–67. CrossRefPubMed
2.
go back to reference Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS. Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontology. 2000;1997(14):216–48. Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS. Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontology. 2000;1997(14):216–48.
3.
go back to reference Albandar JM. Epidemiology and risk factors of periodontal diseases. Dent Clin N Am 2005;49(3):517–32, v–vi. Albandar JM. Epidemiology and risk factors of periodontal diseases. Dent Clin N Am 2005;49(3):517–32, v–vi.
4.
go back to reference Gross AJ, Paskett KT, Cheever VJ, Lipsky MS. Periodontitis: a global disease and the primary care provider’s role. Postgrad Med J. 2017;93(1103):560–5. CrossRefPubMed Gross AJ, Paskett KT, Cheever VJ, Lipsky MS. Periodontitis: a global disease and the primary care provider’s role. Postgrad Med J. 2017;93(1103):560–5. CrossRefPubMed
5.
go back to reference Ling MR, Chapple IL, Matthews JB. Peripheral blood neutrophil cytokine hyper-reactivity in chronic periodontitis. Innate Immun. 2015;21(7):714–25. CrossRefPubMed Ling MR, Chapple IL, Matthews JB. Peripheral blood neutrophil cytokine hyper-reactivity in chronic periodontitis. Innate Immun. 2015;21(7):714–25. CrossRefPubMed
6.
go back to reference Abe T, AlSarhan M, Benakanakere MR, Maekawa T, Kinane DF, Cancro MP, et al. The B cell-stimulatory cytokines BLyS and APRIL are elevated in human periodontitis and are required for B cell-dependent bone loss in experimental murine periodontitis. J Immunol. 2015;195(4):1427–35. CrossRefPubMed Abe T, AlSarhan M, Benakanakere MR, Maekawa T, Kinane DF, Cancro MP, et al. The B cell-stimulatory cytokines BLyS and APRIL are elevated in human periodontitis and are required for B cell-dependent bone loss in experimental murine periodontitis. J Immunol. 2015;195(4):1427–35. CrossRefPubMed
7.
go back to reference Zhu LF, Li L, Wang XQ, Pan L, Mei YM, Fu YW, et al. M1 macrophages regulate TLR4/AP1 via paracrine to promote alveolar bone destruction in periodontitis. Oral Dis. 2019;25(8):1972–82. CrossRefPubMed Zhu LF, Li L, Wang XQ, Pan L, Mei YM, Fu YW, et al. M1 macrophages regulate TLR4/AP1 via paracrine to promote alveolar bone destruction in periodontitis. Oral Dis. 2019;25(8):1972–82. CrossRefPubMed
8.
go back to reference Dutzan N, Kajikawa T, Abusleme L, Greenwell-Wild T, Zuazo CE, Ikeuchi T, et al. A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018;10(463):eaat0797. CrossRefPubMedPubMedCentral Dutzan N, Kajikawa T, Abusleme L, Greenwell-Wild T, Zuazo CE, Ikeuchi T, et al. A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018;10(463):eaat0797. CrossRefPubMedPubMedCentral
10.
go back to reference Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497–506. CrossRefPubMedPubMedCentral Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497–506. CrossRefPubMedPubMedCentral
11.
12.
go back to reference Brecx MC, Fröhlicher I, Gehr P, Lang NP. Stereological observations on long-term experimental gingivitis in man. J Clin Periodontol. 1988;15(10):621–7. CrossRefPubMed Brecx MC, Fröhlicher I, Gehr P, Lang NP. Stereological observations on long-term experimental gingivitis in man. J Clin Periodontol. 1988;15(10):621–7. CrossRefPubMed
13.
go back to reference Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA. Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol Biol. 2018;1711:243–59. CrossRefPubMedPubMedCentral Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA. Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol Biol. 2018;1711:243–59. CrossRefPubMedPubMedCentral
14.
go back to reference Rohr-Udilova N, Klinglmuller F, Schulte-Hermann R, Stift J, Herac M, Salzmann M, et al. Deviations of the immune cell landscape between healthy liver and hepatocellular carcinoma. Sci Rep. 2018;8(1):6220. CrossRefPubMedPubMedCentral Rohr-Udilova N, Klinglmuller F, Schulte-Hermann R, Stift J, Herac M, Salzmann M, et al. Deviations of the immune cell landscape between healthy liver and hepatocellular carcinoma. Sci Rep. 2018;8(1):6220. CrossRefPubMedPubMedCentral
15.
go back to reference Nirmal AJ, Regan T, Shih BB, Hume DA, Sims AH, Freeman TC. Immune cell gene signatures for profiling the microenvironment of solid tumors. Cancer Immunol Res. 2018;6(11):1388–400. CrossRefPubMed Nirmal AJ, Regan T, Shih BB, Hume DA, Sims AH, Freeman TC. Immune cell gene signatures for profiling the microenvironment of solid tumors. Cancer Immunol Res. 2018;6(11):1388–400. CrossRefPubMed
16.
go back to reference Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7. CrossRefPubMedPubMedCentral Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7. CrossRefPubMedPubMedCentral
17.
go back to reference Demmer RT, Behle JH, Wolf DL, Handfield M, Kebschull M, Celenti R, et al. Transcriptomes in healthy and diseased gingival tissues. J Periodontol. 2008;79(11):2112–24. CrossRefPubMedPubMedCentral Demmer RT, Behle JH, Wolf DL, Handfield M, Kebschull M, Celenti R, et al. Transcriptomes in healthy and diseased gingival tissues. J Periodontol. 2008;79(11):2112–24. CrossRefPubMedPubMedCentral
18.
go back to reference Papapanou PN, Behle JH, Kebschull M, Celenti R, Wolf DL, Handfield M, et al. Subgingival bacterial colonization profiles correlate with gingival tissue gene expression. BMC Microbiol. 2009;9:221. CrossRefPubMedPubMedCentral Papapanou PN, Behle JH, Kebschull M, Celenti R, Wolf DL, Handfield M, et al. Subgingival bacterial colonization profiles correlate with gingival tissue gene expression. BMC Microbiol. 2009;9:221. CrossRefPubMedPubMedCentral
19.
go back to reference Abe D, Kubota T, Morozumi T, Shimizu T, Nakasone N, Itagaki M, et al. Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues. J Periodontal Res. 2011;46(3):345–53. CrossRefPubMed Abe D, Kubota T, Morozumi T, Shimizu T, Nakasone N, Itagaki M, et al. Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues. J Periodontal Res. 2011;46(3):345–53. CrossRefPubMed
20.
21.
go back to reference Zhang Z, Yuan W, Deng J, Wang D, Zhang T, Peng L, et al. Granulocyte colony stimulating factor (G-CSF) regulates neutrophils infiltration and periodontal tissue destruction in an experimental periodontitis. Mol Immunol. 2020;117:110–21. CrossRefPubMed Zhang Z, Yuan W, Deng J, Wang D, Zhang T, Peng L, et al. Granulocyte colony stimulating factor (G-CSF) regulates neutrophils infiltration and periodontal tissue destruction in an experimental periodontitis. Mol Immunol. 2020;117:110–21. CrossRefPubMed
22.
go back to reference Mahanonda R, Champaiboon C, Subbalekha K, Sa-Ard-Iam N, Yongyuth A, Isaraphithakkul B, et al. Memory T cell subsets in healthy gingiva and periodontitis tissues. J Periodontol. 2018;89(9):1121–30. CrossRefPubMed Mahanonda R, Champaiboon C, Subbalekha K, Sa-Ard-Iam N, Yongyuth A, Isaraphithakkul B, et al. Memory T cell subsets in healthy gingiva and periodontitis tissues. J Periodontol. 2018;89(9):1121–30. CrossRefPubMed
23.
go back to reference Dutzan N, Konkel JE, Greenwell-Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol. 2016;9(5):1163–72. CrossRefPubMedPubMedCentral Dutzan N, Konkel JE, Greenwell-Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol. 2016;9(5):1163–72. CrossRefPubMedPubMedCentral
24.
go back to reference Xiong Y, Wang K, Zhou H, Peng L, You W, Fu Z. Profiles of immune infiltration in colorectal cancer and their clinical significant: a gene expression-based study. Cancer Med. 2018;7(9):4496–508. CrossRefPubMedPubMedCentral Xiong Y, Wang K, Zhou H, Peng L, You W, Fu Z. Profiles of immune infiltration in colorectal cancer and their clinical significant: a gene expression-based study. Cancer Med. 2018;7(9):4496–508. CrossRefPubMedPubMedCentral
25.
go back to reference Thorbert-Mros S, Larsson L, Berglundh T. Cellular composition of long-standing gingivitis and periodontitis lesions. J Periodontal Res. 2015;50(4):535–43. CrossRefPubMed Thorbert-Mros S, Larsson L, Berglundh T. Cellular composition of long-standing gingivitis and periodontitis lesions. J Periodontal Res. 2015;50(4):535–43. CrossRefPubMed
26.
go back to reference Czerkinsky C, Rees AS, Bergmeier LA, Challacombe SJ. The detection and specificity of class specific antibodies to whole bacterial cells using a solid phase radioimmunoassay. Clin Exp Immunol. 1983;53(1):192–200. PubMedPubMedCentral Czerkinsky C, Rees AS, Bergmeier LA, Challacombe SJ. The detection and specificity of class specific antibodies to whole bacterial cells using a solid phase radioimmunoassay. Clin Exp Immunol. 1983;53(1):192–200. PubMedPubMedCentral
27.
go back to reference Czerkinsky C, Prince SJ, Michalek SM, Jackson S, Russell MW, Moldoveanu Z, McGhee JR, Mestecky J. IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans. Proc Natl Acad Sci U S A. 1987;84(8):2449–53. CrossRefPubMedPubMedCentral Czerkinsky C, Prince SJ, Michalek SM, Jackson S, Russell MW, Moldoveanu Z, McGhee JR, Mestecky J. IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans. Proc Natl Acad Sci U S A. 1987;84(8):2449–53. CrossRefPubMedPubMedCentral
28.
go back to reference Czerkinsky C, Nilsson LA, Ouchterlony O, Tarkowski A, Gretzer C. Detection of single antibody-secreting cells generated after in vitro antigen-induced stimulation of human peripheral blood lymphocytes. Scand J Immunol. 1984;19(6):575–9. CrossRefPubMed Czerkinsky C, Nilsson LA, Ouchterlony O, Tarkowski A, Gretzer C. Detection of single antibody-secreting cells generated after in vitro antigen-induced stimulation of human peripheral blood lymphocytes. Scand J Immunol. 1984;19(6):575–9. CrossRefPubMed
29.
go back to reference Sedgwick JD, Holt PG. Kinetics and distribution of antigen-specific IgE-secreting cells during the primary antibody response in the rat. J Exp Med. 1983;157(6):2178–83. CrossRefPubMed Sedgwick JD, Holt PG. Kinetics and distribution of antigen-specific IgE-secreting cells during the primary antibody response in the rat. J Exp Med. 1983;157(6):2178–83. CrossRefPubMed
30.
go back to reference Holt PG, Sedgwick JD, O’Leary C, Krska K, Leivers S. Long-lived IgE- and IgG-secreting cells in rodents manifesting persistent antibody responses. Cell Immunol. 1984;89(2):281–9. CrossRefPubMed Holt PG, Sedgwick JD, O’Leary C, Krska K, Leivers S. Long-lived IgE- and IgG-secreting cells in rodents manifesting persistent antibody responses. Cell Immunol. 1984;89(2):281–9. CrossRefPubMed
31.
go back to reference Mizutani Y, Shiogama K, Onouchi T, Sakurai K, Inada K, Tsutsumi Y. Enzyme-labeled antigen method: development and application of the novel approach for identifying plasma cells locally producing disease-specific antibodies in inflammatory lesions. Acta Histochem Cytochem. 2016;49(1):7–19. CrossRefPubMedPubMedCentral Mizutani Y, Shiogama K, Onouchi T, Sakurai K, Inada K, Tsutsumi Y. Enzyme-labeled antigen method: development and application of the novel approach for identifying plasma cells locally producing disease-specific antibodies in inflammatory lesions. Acta Histochem Cytochem. 2016;49(1):7–19. CrossRefPubMedPubMedCentral
32.
go back to reference Mizutani Y, Tsuge S, Takeda H, Hasegawa Y, Shiogama K, Onouchi T, et al. In situ visualization of plasma cells producing antibodies reactive to Porphyromonas gingivalis in periodontitis: the application of the enzyme-labeled antigen method. Mol Oral Microbiol. 2014;29(4):156–73. CrossRefPubMedPubMedCentral Mizutani Y, Tsuge S, Takeda H, Hasegawa Y, Shiogama K, Onouchi T, et al. In situ visualization of plasma cells producing antibodies reactive to Porphyromonas gingivalis in periodontitis: the application of the enzyme-labeled antigen method. Mol Oral Microbiol. 2014;29(4):156–73. CrossRefPubMedPubMedCentral
33.
go back to reference Pelletier N, McHeyzer-Williams LJ, Wong KA, Urich E, Fazilleau N, McHeyzer-Williams MG. Plasma cells negatively regulate the follicular helper T cell program. Nat Immunol. 2010;11(12):1110–8. CrossRefPubMedPubMedCentral Pelletier N, McHeyzer-Williams LJ, Wong KA, Urich E, Fazilleau N, McHeyzer-Williams MG. Plasma cells negatively regulate the follicular helper T cell program. Nat Immunol. 2010;11(12):1110–8. CrossRefPubMedPubMedCentral
34.
go back to reference Shen P, Roch T, Lampropoulou V, O’Connor RA, Stervbo U, Hilgenberg E, et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature. 2014;507(7492):366–70. CrossRefPubMedPubMedCentral Shen P, Roch T, Lampropoulou V, O’Connor RA, Stervbo U, Hilgenberg E, et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature. 2014;507(7492):366–70. CrossRefPubMedPubMedCentral
35.
go back to reference Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014;20(6):633–41. CrossRefPubMedPubMedCentral Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014;20(6):633–41. CrossRefPubMedPubMedCentral
36.
go back to reference Jing L, Kim S, Sun L, Wang L, Mildner E, Divaris K, et al. IL-37- and IL-35/IL-37-producing plasma cells in chronic periodontitis. J Dent Res. 2019;98(7):813–21. CrossRefPubMedPubMedCentral Jing L, Kim S, Sun L, Wang L, Mildner E, Divaris K, et al. IL-37- and IL-35/IL-37-producing plasma cells in chronic periodontitis. J Dent Res. 2019;98(7):813–21. CrossRefPubMedPubMedCentral
37.
go back to reference Shen P, Fillatreau S. Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol. 2015;15(7):441–51. CrossRefPubMed Shen P, Fillatreau S. Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol. 2015;15(7):441–51. CrossRefPubMed
38.
go back to reference Mahanonda R, Champaiboon C, Subbalekha K, Sa-Ard-Iam N, Rattanathammatada W, Thawanaphong S, et al. Human memory B cells in healthy gingiva, gingivitis, and periodontitis. J Immunol. 2016;197(3):715–25. CrossRefPubMed Mahanonda R, Champaiboon C, Subbalekha K, Sa-Ard-Iam N, Rattanathammatada W, Thawanaphong S, et al. Human memory B cells in healthy gingiva, gingivitis, and periodontitis. J Immunol. 2016;197(3):715–25. CrossRefPubMed
39.
go back to reference Han Y, Jin Y, Miao Y, Shi T, Lin X. Improved RANKL expression and osteoclastogenesis induction of CD27+CD38- memory B cells: a link between B cells and alveolar bone damage in periodontitis. J Periodontal Res. 2019;54(1):73–80. CrossRefPubMed Han Y, Jin Y, Miao Y, Shi T, Lin X. Improved RANKL expression and osteoclastogenesis induction of CD27+CD38- memory B cells: a link between B cells and alveolar bone damage in periodontitis. J Periodontal Res. 2019;54(1):73–80. CrossRefPubMed
40.
go back to reference Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20. CrossRefPubMedPubMedCentral Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20. CrossRefPubMedPubMedCentral
41.
go back to reference Sima C, Glogauer M. Macrophage subsets and osteoimmunology: tuning of the immunological recognition and effector systems that maintain alveolar bone. Periodontology 2000. 2013;63(1):80–101. CrossRefPubMed Sima C, Glogauer M. Macrophage subsets and osteoimmunology: tuning of the immunological recognition and effector systems that maintain alveolar bone. Periodontology 2000. 2013;63(1):80–101. CrossRefPubMed
Metadata
Title
Differential immune cell infiltrations between healthy periodontal and chronic periodontitis tissues
Authors
Wei Li
Zheng Zhang
Zuo-min Wang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2020
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-020-01287-0

Other articles of this Issue 1/2020

BMC Oral Health 1/2020 Go to the issue