Skip to main content
Top
Published in: BMC Oral Health 1/2019

Open Access 01-12-2019 | Research article

Nasal double DNA adjuvant induces salivary FimA-specific secretory IgA antibodies in young and aging mice and blocks Porphyromonas gingivalis binding to a salivary protein

Authors: Kenjiro Kobuchi, Kosuke Kataoka, Yoichiro Taguchi, Tatsuro Miyake, Makoto Umeda

Published in: BMC Oral Health | Issue 1/2019

Login to get access

Abstract

Background

We previously showed that nasal administration of a combination of dendritic cell (DC) targeted DNA plasmid expressing Flt3 ligand and CpG oligodeoxynucleotides 1826 as a mucosal adjuvant (double adjuvant, DA) provoked protective immunity in the upper respiratory tract of young adult and aging mice. Here, we investigated whether the nasal DA system induces secretory (S)IgA antibodies (Abs) toward recombinant fimbrillin (rFimA) of Porphyromonas gingivalis (P. gingivalis) in the saliva of young adult and aging mice. Further, we examined the functional applicability of rFimA-specific salivary SIgA Abs.

Methods

BALB/c mice (8- or 48-week-old) were nasally immunized with rFimA plus DA three times at weekly intervals. Control mice were nasally administered rFimA alone. Saliva samples were collected 1 week after the final immunization, and were subjected to rFimA-specific ELISA. To examine the functional applicability of rFimA-specific SIgA Abs, IgA-enriched saliva samples were subjected to an inhibition assay in order to assess the numbers of P. gingivalis cells bound to the salivary protein statherin.

Results

The 8- and 48-week-old mice administered nasal rFimA plus DA showed significantly increased levels of rFimA-specific SIgA Abs in saliva and elevated numbers of CD11c+ DCs in sublingual glands (SLGs), periglandular lymph nodes (PGLNs) and submandibular glands (SMGs) as well as nasopharyngeal-associated lymphoid tissues (NALT) compared to mice administered rFimA alone. Further, rFimA-specific SIgA Abs-containing saliva, in which IgG Abs of 8- and 48-week-old mice administered nasal rFimA plus DA were removed, significantly inhibited binding of P. gingivalis to the salivary protein.

Conclusions

These findings show that this DA system could be an effective nasal vaccine strategy for the enhancement of P. gingivalis-specific protective immunity in the oral cavity of adolescents and older individuals.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gibbons RJ, Macdonald JB. Hemin and vitamin K compounds as required factors for the cultivation of certain strains of Bacteroides melaninogenicus. J BacteriolJ Bacteriol. 1960;80:164–70. Gibbons RJ, Macdonald JB. Hemin and vitamin K compounds as required factors for the cultivation of certain strains of Bacteroides melaninogenicus. J BacteriolJ Bacteriol. 1960;80:164–70.
2.
go back to reference Mayrand D, Holt SC. Biology of asaccharolytic black-pigmented Bacteroides species. Microbiol RevMicrobiol Rev. 1988;52:134–52. Mayrand D, Holt SC. Biology of asaccharolytic black-pigmented Bacteroides species. Microbiol RevMicrobiol Rev. 1988;52:134–52.
3.
go back to reference Totaro MC, Cattani P, Ria F, Tolusso B, Gremese E, Fedele AL, D’Onghia S, Marchetti S, Di Sante G, Canestri S, Ferraccioli G. Porphyromonas gingivalis and the pathogenesis of rheumatoid arthritis: analysis of various compartments including the synovial tissue. Arthritis Res Ther. 2013;15:R66.CrossRef Totaro MC, Cattani P, Ria F, Tolusso B, Gremese E, Fedele AL, D’Onghia S, Marchetti S, Di Sante G, Canestri S, Ferraccioli G. Porphyromonas gingivalis and the pathogenesis of rheumatoid arthritis: analysis of various compartments including the synovial tissue. Arthritis Res Ther. 2013;15:R66.CrossRef
4.
go back to reference Serra e Silva Filho W, Casarin RC, Nicolela EL Jr, Passos HM, Sallum AW, Goncalves RB. Microbial diversity similarities in periodontal pockets and atheromatous plaques of cardiovascular disease patients. PLoS One. 2014;16:e109761.CrossRef Serra e Silva Filho W, Casarin RC, Nicolela EL Jr, Passos HM, Sallum AW, Goncalves RB. Microbial diversity similarities in periodontal pockets and atheromatous plaques of cardiovascular disease patients. PLoS One. 2014;16:e109761.CrossRef
5.
go back to reference Haffajee AD, Cugini MA, Tanner A, Pollack RP, Smith C, Kent RL Jr, Socransky SS. Subgingival microbiota in healthy, well-maintained elder and periodontitis subjects. J Clin Periodontol. 1998;25:346–53.CrossRef Haffajee AD, Cugini MA, Tanner A, Pollack RP, Smith C, Kent RL Jr, Socransky SS. Subgingival microbiota in healthy, well-maintained elder and periodontitis subjects. J Clin Periodontol. 1998;25:346–53.CrossRef
6.
go back to reference How KY, Song KP, Chan KG. Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front MicrobiolFront Microbiol. 2016;7:53. How KY, Song KP, Chan KG. Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front MicrobiolFront Microbiol. 2016;7:53.
7.
go back to reference Kataoka K, Amano A, Kuboniwa M, Horie H, Nagata H, Shizukuishi S. Active sited of salivary proline-rich protein for binding to Porphyromonas gingivalis fimbriae. Infect ImmunInfect Immun. 1997;65:3159–64. Kataoka K, Amano A, Kuboniwa M, Horie H, Nagata H, Shizukuishi S. Active sited of salivary proline-rich protein for binding to Porphyromonas gingivalis fimbriae. Infect ImmunInfect Immun. 1997;65:3159–64.
8.
go back to reference Hospenthal MK, Costa TRD, Waksman G. A comprehensive guide to pilous biogenesis in gram-negative bacteria. Nat Rev Microbiol. 2017;15:365–79.CrossRef Hospenthal MK, Costa TRD, Waksman G. A comprehensive guide to pilous biogenesis in gram-negative bacteria. Nat Rev Microbiol. 2017;15:365–79.CrossRef
9.
go back to reference Lamont RJ, Jenkinson HF. Subgingival colonization by Porphyromonas gingivalis. Oral Microbiol ImmunolOral Microbiol Immunol. 2000;15:341–9.CrossRef Lamont RJ, Jenkinson HF. Subgingival colonization by Porphyromonas gingivalis. Oral Microbiol ImmunolOral Microbiol Immunol. 2000;15:341–9.CrossRef
10.
go back to reference Yoshimura F, Takahashi K, Nodasaka Y, Suzuki T. Purification and characterization of a novel type of fimbriae from the oral anaerobe Bacteroides gingivalis. J BacteriolJ Bacteriol. 1984;160:949–57. Yoshimura F, Takahashi K, Nodasaka Y, Suzuki T. Purification and characterization of a novel type of fimbriae from the oral anaerobe Bacteroides gingivalis. J BacteriolJ Bacteriol. 1984;160:949–57.
11.
go back to reference Hamada S, Amano A, Kimura S, Nakagawa I, Kawabata S, Morisaki I. The importance of fimbriae in the virulence and ecology of some oral bacteria. Oral Microbiol ImmunolOral Microbiol Immunol. 1998;13:129–38.CrossRef Hamada S, Amano A, Kimura S, Nakagawa I, Kawabata S, Morisaki I. The importance of fimbriae in the virulence and ecology of some oral bacteria. Oral Microbiol ImmunolOral Microbiol Immunol. 1998;13:129–38.CrossRef
12.
go back to reference Cai J, Chen J, Guo H, Pan Y, Zhang Y, Zhao W, Li X, Li Y. Recombinant fimbriae protein of Porphyromonas gingivalis induces an inflammatory responses via the TLR4/NF-kB signaling pathway in human peripheral blood mononuclear cells. Int J Mol MedInt J Mol Med. 2019;43:1430–40. Cai J, Chen J, Guo H, Pan Y, Zhang Y, Zhao W, Li X, Li Y. Recombinant fimbriae protein of Porphyromonas gingivalis induces an inflammatory responses via the TLR4/NF-kB signaling pathway in human peripheral blood mononuclear cells. Int J Mol MedInt J Mol Med. 2019;43:1430–40.
13.
go back to reference Amano A, Kataoka K, Raj PA, Genco RJ, Shizukuishi S. Binding sites of salivary statherin for Porphyromonas gingivalis recombinant fimbrillin. Infect ImmunInfect Immun. 1996;64:4249–54. Amano A, Kataoka K, Raj PA, Genco RJ, Shizukuishi S. Binding sites of salivary statherin for Porphyromonas gingivalis recombinant fimbrillin. Infect ImmunInfect Immun. 1996;64:4249–54.
14.
go back to reference Mestecky J. The mucosal immune system. In: Paul WE, editor. Fundamental immunology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2003. p. 965–1020. Mestecky J. The mucosal immune system. In: Paul WE, editor. Fundamental immunology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2003. p. 965–1020.
15.
go back to reference Briles DE, Ades E, Paton JC, Sampson JS, Carlone GM, Huebner RC, Virolainen A, Swiatlo E, Hollingshead SK. Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective adjuvant nasopharyngeal carriage of Streptococcus pneumoniae. Infect ImmunInfect Immun. 2000;68:796–800.CrossRef Briles DE, Ades E, Paton JC, Sampson JS, Carlone GM, Huebner RC, Virolainen A, Swiatlo E, Hollingshead SK. Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective adjuvant nasopharyngeal carriage of Streptococcus pneumoniae. Infect ImmunInfect Immun. 2000;68:796–800.CrossRef
16.
go back to reference Imaoka K, Miller CJ, Kubota M, McChesney MB, Lohman B, Yamamoto M, Fujihashi K, Someya K, Honda M, McGhee JR, Kiyono H. Nasal immunization of nonhuman primates with simian immunodeficiency virus p55 gag and cholera toxin adjuvant induces Th1/Th2 help for virus-specific immune responses in reproductive tissues. J ImmunolJ Immunol. 1998;161:5952–8. Imaoka K, Miller CJ, Kubota M, McChesney MB, Lohman B, Yamamoto M, Fujihashi K, Someya K, Honda M, McGhee JR, Kiyono H. Nasal immunization of nonhuman primates with simian immunodeficiency virus p55 gag and cholera toxin adjuvant induces Th1/Th2 help for virus-specific immune responses in reproductive tissues. J ImmunolJ Immunol. 1998;161:5952–8.
17.
go back to reference Hagiwara Y, McGhee JR, Fujihashi K, Kobayashi R, Yoshino N, Kataoka K, Etani Y, Kweon MN, Tamura S, Kurata T, Takeda Y, Kiyono H. Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissues. J ImmunolJ Immunol. 2003;170:1754–62.CrossRef Hagiwara Y, McGhee JR, Fujihashi K, Kobayashi R, Yoshino N, Kataoka K, Etani Y, Kweon MN, Tamura S, Kurata T, Takeda Y, Kiyono H. Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissues. J ImmunolJ Immunol. 2003;170:1754–62.CrossRef
18.
go back to reference Langermann S, Palaszynsky S, Sadzience A, Stover C, Koenig S. Systemic and mucosal immunity induced by BCG vector expressing outer-surface protein a of Borrelia burgdorferi. Nature. 1994;372:552–5.CrossRef Langermann S, Palaszynsky S, Sadzience A, Stover C, Koenig S. Systemic and mucosal immunity induced by BCG vector expressing outer-surface protein a of Borrelia burgdorferi. Nature. 1994;372:552–5.CrossRef
19.
go back to reference Vadolas J, Davies JK, Wright PJ, Strugnell RA. Intranasal immunization with liposomes induces strong mucosal immune responses in mice. Eur J ImmunolEur J Immunol. 1995;25:969–75.CrossRef Vadolas J, Davies JK, Wright PJ, Strugnell RA. Intranasal immunization with liposomes induces strong mucosal immune responses in mice. Eur J ImmunolEur J Immunol. 1995;25:969–75.CrossRef
20.
go back to reference Kataoka K, McGhee JR, Kobayashi R, Fujihashi K, Shizukuishi S, Fujihashi K. Nasal Flt3 ligand cDNA elicits CD11c+ CD8+ dendritic cells for enhanced mucosal immunity. J ImmunolJ Immunol. 2004;172:3612–9.CrossRef Kataoka K, McGhee JR, Kobayashi R, Fujihashi K, Shizukuishi S, Fujihashi K. Nasal Flt3 ligand cDNA elicits CD11c+ CD8+ dendritic cells for enhanced mucosal immunity. J ImmunolJ Immunol. 2004;172:3612–9.CrossRef
21.
go back to reference Kataoka K, Fujihashi K. Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines. Expert Rev Vaccines. 2009;8:1183–93.CrossRef Kataoka K, Fujihashi K. Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines. Expert Rev Vaccines. 2009;8:1183–93.CrossRef
22.
go back to reference Fukuiwa T, Sekine S, Kobayashi R, Suzuki H, Kataoka K, Gilbert RS, Kurono Y, Boyaka PN, Kreig AM, McGhee JR, Fujihashi K. A recombination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity. Vaccine. 2008;26:4849–59.CrossRef Fukuiwa T, Sekine S, Kobayashi R, Suzuki H, Kataoka K, Gilbert RS, Kurono Y, Boyaka PN, Kreig AM, McGhee JR, Fujihashi K. A recombination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity. Vaccine. 2008;26:4849–59.CrossRef
23.
go back to reference Kataoka K, Fukuyama Y, Briles DE, Miyake T, Fujihashi K. Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae. Microbiol ImmunolMicrobiol Immunol. 2017;61:195–205.CrossRef Kataoka K, Fukuyama Y, Briles DE, Miyake T, Fujihashi K. Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae. Microbiol ImmunolMicrobiol Immunol. 2017;61:195–205.CrossRef
24.
go back to reference Challacombe SJ. Immunology of Diseases of the Oral Cavity. In: Mestecky J, editor. Mucosal Immunology. 4th ed. Oxford: Elsevier; 2015. p. 1943–84.CrossRef Challacombe SJ. Immunology of Diseases of the Oral Cavity. In: Mestecky J, editor. Mucosal Immunology. 4th ed. Oxford: Elsevier; 2015. p. 1943–84.CrossRef
25.
go back to reference Ebersole JL, Taubman MA, Smith DM, Frey DE. Human responses to microorganisms: pattern of systemic antibody level to Bacteroides species. Infect ImmunInfect Immun. 1986;51:507–13. Ebersole JL, Taubman MA, Smith DM, Frey DE. Human responses to microorganisms: pattern of systemic antibody level to Bacteroides species. Infect ImmunInfect Immun. 1986;51:507–13.
26.
go back to reference Plombas M, Gobert B, De March AK, Kolopp Sarda MN, Sixou M, Bene MC, Miller N, Faure GC. Isotype antibody response to plaque anaerobes in periodontal disease. J PeriodontolJ Periodontol. 2002;73:1507–11.CrossRef Plombas M, Gobert B, De March AK, Kolopp Sarda MN, Sixou M, Bene MC, Miller N, Faure GC. Isotype antibody response to plaque anaerobes in periodontal disease. J PeriodontolJ Periodontol. 2002;73:1507–11.CrossRef
27.
go back to reference Chen HA, Johnson BD, Sims TJ, Darveau RP, Moncla BJ, Whitney CW, Engel D, Page RC. Humoral immune responses to Porphyromonas gingivalis before and following therapy in rapidly progressive periodontitis patients. J PeriodontolJ Periodontol. 1991;62:781–91.CrossRef Chen HA, Johnson BD, Sims TJ, Darveau RP, Moncla BJ, Whitney CW, Engel D, Page RC. Humoral immune responses to Porphyromonas gingivalis before and following therapy in rapidly progressive periodontitis patients. J PeriodontolJ Periodontol. 1991;62:781–91.CrossRef
28.
go back to reference Kawabata S, Terao Y, Fujiwara T, Nakagawa I, Hamada S. Targeted salivary gland immunization with plasmid DNA elicits specific salivary immunoglobulin a and G antibodies and serum immunoglobulin G antibodies in mice. Infect ImmunInfect Immun. 1999;67:5863–8. Kawabata S, Terao Y, Fujiwara T, Nakagawa I, Hamada S. Targeted salivary gland immunization with plasmid DNA elicits specific salivary immunoglobulin a and G antibodies and serum immunoglobulin G antibodies in mice. Infect ImmunInfect Immun. 1999;67:5863–8.
29.
go back to reference Fujiwara T, Morishima S, Takahashi I, Hamada S. Molecular cloning and sequencing of fimbrillin gene of Porphyromonas gingivalis strains and characterization of recombinant proteins. Biochem Biophys Res CommunBiochem Biophys Res Commun. 1993;197:241–7.CrossRef Fujiwara T, Morishima S, Takahashi I, Hamada S. Molecular cloning and sequencing of fimbrillin gene of Porphyromonas gingivalis strains and characterization of recombinant proteins. Biochem Biophys Res CommunBiochem Biophys Res Commun. 1993;197:241–7.CrossRef
30.
go back to reference Fukuyama Y, King JD, Kataoka K, Kobayashi R, Gilbert RS, Hollingshead SK, Briles DE, Fujihashi K. A combination of Flt3 ligand cDNA and CpG oligodeoxynucleotide as nasal adjuvant elicits protective secretory-IgA immunity to Streptococcus pneumoniae in aged mice. J ImmunolJ Immunol. 2011;186:2454–61.CrossRef Fukuyama Y, King JD, Kataoka K, Kobayashi R, Gilbert RS, Hollingshead SK, Briles DE, Fujihashi K. A combination of Flt3 ligand cDNA and CpG oligodeoxynucleotide as nasal adjuvant elicits protective secretory-IgA immunity to Streptococcus pneumoniae in aged mice. J ImmunolJ Immunol. 2011;186:2454–61.CrossRef
31.
go back to reference Kataoka K, Fujihashi K, Sekine S, Fukuiwa T, Kobayashi R, Suzuki H, Nagata H, Takatsu K, Shizukusihi S, McGhee JR, Fujihashi K. Nasal cholera toxin elicits IL-5 and IL-5 receptor α-chain expressing B-1a B cells for innate mucosal IgA antibody responses. J ImmunolJ Immunol. 2007;178:6058–65.CrossRef Kataoka K, Fujihashi K, Sekine S, Fukuiwa T, Kobayashi R, Suzuki H, Nagata H, Takatsu K, Shizukusihi S, McGhee JR, Fujihashi K. Nasal cholera toxin elicits IL-5 and IL-5 receptor α-chain expressing B-1a B cells for innate mucosal IgA antibody responses. J ImmunolJ Immunol. 2007;178:6058–65.CrossRef
32.
go back to reference Mega J, McGhee JR, Kiyono H. Cytokine-and Ig-producing cells in mucosal effector tissues: analysis of IL-5- and IFN-γ-producing T cells, T cell receptor expression, and IgA plasma cells from mouse salivary gland-associated tissues. J ImmunolJ Immunol. 1992;148:2030–9. Mega J, McGhee JR, Kiyono H. Cytokine-and Ig-producing cells in mucosal effector tissues: analysis of IL-5- and IFN-γ-producing T cells, T cell receptor expression, and IgA plasma cells from mouse salivary gland-associated tissues. J ImmunolJ Immunol. 1992;148:2030–9.
33.
go back to reference Persson GR. Periodontal complications with age. Periodontol 2000. 2018;78:185–94.CrossRef Persson GR. Periodontal complications with age. Periodontol 2000. 2018;78:185–94.CrossRef
34.
go back to reference Kinoshita M, Yokote K, Arai H, Iida H, Ishigaki Y, Ishibashi S, Umemoto S, Egusa G, Ohmura H, Okamura T, Kihara S, Koba S, Saito I, Shoji T, Daida H, Tsukamoto K, Deguchi J, Dohi S, Dobashi K, Hamaguchi H, Hara M, Hiro T, Biro S, Fujioka Y, Maruyama C, Miyamoto Y, Murakami Y, Yokode M, Yoshida H, Rakugi H, Wakatsuki A, Yamashita S, Committee for Epidemiology and Clinical Management of Atherosclerosis. Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017. J Atheroscler ThrombJ Atheroscler Thromb. 2018;25:846–984.CrossRef Kinoshita M, Yokote K, Arai H, Iida H, Ishigaki Y, Ishibashi S, Umemoto S, Egusa G, Ohmura H, Okamura T, Kihara S, Koba S, Saito I, Shoji T, Daida H, Tsukamoto K, Deguchi J, Dohi S, Dobashi K, Hamaguchi H, Hara M, Hiro T, Biro S, Fujioka Y, Maruyama C, Miyamoto Y, Murakami Y, Yokode M, Yoshida H, Rakugi H, Wakatsuki A, Yamashita S, Committee for Epidemiology and Clinical Management of Atherosclerosis. Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017. J Atheroscler ThrombJ Atheroscler Thromb. 2018;25:846–984.CrossRef
35.
go back to reference Yoon YS, Jin M, Sin DD. Accelerated lung aging and chronic obstructive pulmonary disease. Expert Rev Respir Med. 2019;8:1–12. Yoon YS, Jin M, Sin DD. Accelerated lung aging and chronic obstructive pulmonary disease. Expert Rev Respir Med. 2019;8:1–12.
36.
go back to reference Edwan JH, Perry G, Talmadge JE, Agrawal DK. Flt3-ligand reverses late allergic responses and airway hyper-responsiveness in a mouse model of allergic inflammation. J ImmunolJ Immunol. 2004;172:5016–23.CrossRef Edwan JH, Perry G, Talmadge JE, Agrawal DK. Flt3-ligand reverses late allergic responses and airway hyper-responsiveness in a mouse model of allergic inflammation. J ImmunolJ Immunol. 2004;172:5016–23.CrossRef
37.
go back to reference Kutzler MA, Weiner DB. Developing DNA vaccines that call to dendritic cells. J Clin InvestJ Clin Invest. 2004;114:1241–4.CrossRef Kutzler MA, Weiner DB. Developing DNA vaccines that call to dendritic cells. J Clin InvestJ Clin Invest. 2004;114:1241–4.CrossRef
38.
go back to reference Triccas JA, Shklovskaya E, Spratt J, Ryan AA, Palendira U, et al. Effects of DNA-and Mycobacterium bovis BCG-based delivery of the Flt3 ligand on protective immunity to Mycobacterium tuberculosis. Infect ImmunInfect Immun. 2007;75:5368–75.CrossRef Triccas JA, Shklovskaya E, Spratt J, Ryan AA, Palendira U, et al. Effects of DNA-and Mycobacterium bovis BCG-based delivery of the Flt3 ligand on protective immunity to Mycobacterium tuberculosis. Infect ImmunInfect Immun. 2007;75:5368–75.CrossRef
39.
go back to reference Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukeia. Blood. 2002;100:1532–42.CrossRef Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukeia. Blood. 2002;100:1532–42.CrossRef
40.
go back to reference Marakovsky E, Brasel K, Teepe M, Roux ER, Lyman SD, Shortman K, McKenna HJ. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J Exp MedJ Exp Med. 1996;184:1953–62.CrossRef Marakovsky E, Brasel K, Teepe M, Roux ER, Lyman SD, Shortman K, McKenna HJ. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J Exp MedJ Exp Med. 1996;184:1953–62.CrossRef
41.
go back to reference Fukuyama Y, King JD, Kataoka K, Kobayashi R, Gilbert RS, Hollingshead SK, Briles DE, Fujihashi K. Secretory-IgA plays an important role in the immunity to Streptococcus pneumoniae. J ImmunolJ Immunol. 2010;185:1755–62.CrossRef Fukuyama Y, King JD, Kataoka K, Kobayashi R, Gilbert RS, Hollingshead SK, Briles DE, Fujihashi K. Secretory-IgA plays an important role in the immunity to Streptococcus pneumoniae. J ImmunolJ Immunol. 2010;185:1755–62.CrossRef
42.
go back to reference Fukuyma Y, Ikeda Y, Ohori J, Sugita G, Aso K, Fujihashi K, Briles DE, McGhee JR, Fujihashi K. A molecular mucosal adjuvant to enhance immunity against pneumococcal infection in the elderly. Immune Netw. 2015;15:9–15.CrossRef Fukuyma Y, Ikeda Y, Ohori J, Sugita G, Aso K, Fujihashi K, Briles DE, McGhee JR, Fujihashi K. A molecular mucosal adjuvant to enhance immunity against pneumococcal infection in the elderly. Immune Netw. 2015;15:9–15.CrossRef
43.
go back to reference Asanuma H, Zamri NB, Sekine S, Fukuyama Y, Tokuhara D, Gilbert RS, Fukuiwa T, Fujihashi K, Sata T, Tashiro M, Fujihashi K. A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging. Vaccine. 2012;30:803–12.CrossRef Asanuma H, Zamri NB, Sekine S, Fukuyama Y, Tokuhara D, Gilbert RS, Fukuiwa T, Fujihashi K, Sata T, Tashiro M, Fujihashi K. A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging. Vaccine. 2012;30:803–12.CrossRef
Metadata
Title
Nasal double DNA adjuvant induces salivary FimA-specific secretory IgA antibodies in young and aging mice and blocks Porphyromonas gingivalis binding to a salivary protein
Authors
Kenjiro Kobuchi
Kosuke Kataoka
Yoichiro Taguchi
Tatsuro Miyake
Makoto Umeda
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2019
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-019-0886-2

Other articles of this Issue 1/2019

BMC Oral Health 1/2019 Go to the issue