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Erschienen in: Inflammation Research 1/2021

09.11.2020 | Original Research Paper

Impaired salivary SIgA antibodies elicit oral dysbiosis and subsequent induction of alveolar bone loss

verfasst von: Emily Chang, Ryoki Kobayashi, Kohtaro Fujihashi, Masamichi Komiya, Tomoko Kurita-Ochiai

Erschienen in: Inflammation Research | Ausgabe 1/2021

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Abstract

Objective

Secreted IgA (SIgA) plays a central role in preventing bacterial and viral infections on mucosal surfaces by neutralizing toxins and viruses and inhibiting bacterial attachment to epithelial cells. However, the role of salivary SIgA antibodies (Abs) in regulating oral flora is still unknown. This study aimed to evaluate the association among oral bacteria, their metabolites and periodontitis in IgA-deficient (IgA KO) and wild-type (WT) control mice.

Methods

Microcomputed tomography (micro-CT) analysis was used to assess alveolar bone resorption as a development of periodontitis. The bacterial profiles of saliva were determined using the next-generation sequencing assays. Furthermore, the metabolites in saliva were measured and compared using CE-TOFMS.

Results

Salivary microbiota of IgA KO mice revealed a remarkably decreased frequency of Streptococcus, and increased percentages of Aggregatibacer, Actinobacillus, and Prevotella at the genus level when compared with those of WT. Compared to WT control mice of the same age, the level of alveolar bone loss was significantly increased in IgA KO mice, and infiltration of osteoclasts was found on the surface of the alveolar bone. The metabolome profile indicated that the metabolites of IgA KO mice had greater variability in carbon metabolic, urea cycle, and lipid pathways than WT mice.

Conclusion

These results suggest that salivary SIgA plays an important role in regulating and maintaining normal oral microflora to prevent the development of periodontal disease.
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Literatur
1.
Zurück zum Zitat Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16:745–59.CrossRef Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16:745–59.CrossRef
2.
Zurück zum Zitat Minty M, Canceil T, Serino M, Burcelin R, Terce F, Blasco-Baque V. Oral microbiota-induced periodontitis: a new risk factor of metabolic diseases. Rev Endocr Metab Disord. 2019;20:449–59.CrossRef Minty M, Canceil T, Serino M, Burcelin R, Terce F, Blasco-Baque V. Oral microbiota-induced periodontitis: a new risk factor of metabolic diseases. Rev Endocr Metab Disord. 2019;20:449–59.CrossRef
3.
Zurück zum Zitat Marcotte H, Lavoie MC. Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol Mol Biol Rev. 1998;62:71–109.CrossRef Marcotte H, Lavoie MC. Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol Mol Biol Rev. 1998;62:71–109.CrossRef
4.
Zurück zum Zitat Miletic ID, Schiffman SS, Miletic VD, Sattely-Miller EA. Salivary IgA secretion rate in young and elderly persons. Physiol Behav. 1996;60:243–8.CrossRef Miletic ID, Schiffman SS, Miletic VD, Sattely-Miller EA. Salivary IgA secretion rate in young and elderly persons. Physiol Behav. 1996;60:243–8.CrossRef
5.
Zurück zum Zitat Evans P, Der G, Ford G, Hucklebridge F, Hunt K, Lambert S. Social class, sex, and age differences in mucosal immunity in a large community sample. Brain Behav Immun. 2000;14:41–8.CrossRef Evans P, Der G, Ford G, Hucklebridge F, Hunt K, Lambert S. Social class, sex, and age differences in mucosal immunity in a large community sample. Brain Behav Immun. 2000;14:41–8.CrossRef
6.
Zurück zum Zitat Tanida T, Ueta E, Tobiume A, Hamada T, Rao F, Osaki T. Influence of aging on candidal growth and adhesion regulatory agents in saliva. J Oral Pathol Med. 2001;30:328–35.CrossRef Tanida T, Ueta E, Tobiume A, Hamada T, Rao F, Osaki T. Influence of aging on candidal growth and adhesion regulatory agents in saliva. J Oral Pathol Med. 2001;30:328–35.CrossRef
7.
Zurück zum Zitat Polosukhin VV, Richmond BW, Du RH, Cates JM, Wu P, Nian H, et al. Secretory IgA deficiency in individual small airways is associated with persistent inflammation and remodeling. Am J Respir Crit Care Med. 2017;195:1010–21.CrossRef Polosukhin VV, Richmond BW, Du RH, Cates JM, Wu P, Nian H, et al. Secretory IgA deficiency in individual small airways is associated with persistent inflammation and remodeling. Am J Respir Crit Care Med. 2017;195:1010–21.CrossRef
8.
Zurück zum Zitat Arakawa S, Suzukawa M, Watanabe K, Kobayashi K, Matsui H, Nagai H, et al. Secretory immunoglobulin A induces human lung fibroblasts to produce inflammatory cytokines and undergo activation. Clin Exp Immunol. 2019;195:287–301.CrossRef Arakawa S, Suzukawa M, Watanabe K, Kobayashi K, Matsui H, Nagai H, et al. Secretory immunoglobulin A induces human lung fibroblasts to produce inflammatory cytokines and undergo activation. Clin Exp Immunol. 2019;195:287–301.CrossRef
9.
Zurück zum Zitat Challancombe SJ. Immunology of diseases of the oral cavity. In: Mestecky J, editor. Mucosal Immunology. 4th ed. Oxford: Elsevier; 2015. p. 1943–84.CrossRef Challancombe SJ. Immunology of diseases of the oral cavity. In: Mestecky J, editor. Mucosal Immunology. 4th ed. Oxford: Elsevier; 2015. p. 1943–84.CrossRef
10.
Zurück zum Zitat Kurita-Ochiai T, Hashizume-Takizawa T, Kobayashi R, Yamamoto M. Mucosal vaccines for oral disease. In: Kiyono H, Pascual D, editors. Mucosal vaccines: innovation for preventing infectious disease. Amsterdam: Elsevier/Academic Press; 2019. p. 649–61. Kurita-Ochiai T, Hashizume-Takizawa T, Kobayashi R, Yamamoto M. Mucosal vaccines for oral disease. In: Kiyono H, Pascual D, editors. Mucosal vaccines: innovation for preventing infectious disease. Amsterdam: Elsevier/Academic Press; 2019. p. 649–61.
11.
Zurück zum Zitat Harriman GR, Bogue M, Rogers P, Finegold M, Pacheco S, Bradley A, Zhang Y, Mbawuike IN. Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J Immunol. 1999;162:2521–9.PubMed Harriman GR, Bogue M, Rogers P, Finegold M, Pacheco S, Bradley A, Zhang Y, Mbawuike IN. Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J Immunol. 1999;162:2521–9.PubMed
12.
Zurück zum Zitat Harriman GR, Bradley A, Das S, Rogers-Fani P, Davis AC. IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination. J Clin Invest. 1996;97:477–85.CrossRef Harriman GR, Bradley A, Das S, Rogers-Fani P, Davis AC. IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination. J Clin Invest. 1996;97:477–85.CrossRef
13.
Zurück zum Zitat Ooga T, Sato H, Nagashima A, Sasaki K, Tomita M, Soga T, Ohashi Y. Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia. Mol Biosyst. 2011;7:1217–23.CrossRef Ooga T, Sato H, Nagashima A, Sasaki K, Tomita M, Soga T, Ohashi Y. Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia. Mol Biosyst. 2011;7:1217–23.CrossRef
14.
Zurück zum Zitat Ma J, Li H. The role of gut microbiota in atherosclerosis and hypertension. Front Pharmacol. 2018;9:1082.CrossRef Ma J, Li H. The role of gut microbiota in atherosclerosis and hypertension. Front Pharmacol. 2018;9:1082.CrossRef
15.
Zurück zum Zitat Scannapieco FA, Cantos A. Oral inflammation and infection, and chronic medical diseases: implications for the elderly. Periodontol. 2000;2016(72):153–75. Scannapieco FA, Cantos A. Oral inflammation and infection, and chronic medical diseases: implications for the elderly. Periodontol. 2000;2016(72):153–75.
16.
Zurück zum Zitat Rautava J, Pinnell LJ, Vong L, Akseer N, Assa A, Sherman PM. Oral microbiome composition changes in mouse models of colitis. J Gastroenterol Hepatol. 2015;30:521–7.CrossRef Rautava J, Pinnell LJ, Vong L, Akseer N, Assa A, Sherman PM. Oral microbiome composition changes in mouse models of colitis. J Gastroenterol Hepatol. 2015;30:521–7.CrossRef
17.
Zurück zum Zitat Xiao E, Mattos M, Vieira GHA, Chen S, Correa JD, Wu Y, Albiero ML, Bittinger K, Graves DT. Diabetes enhances IL-17 expression and alters the oral microbiome to increase Its pathogenicity. Cell Host Microbe. 2017;22(120–8):e4. Xiao E, Mattos M, Vieira GHA, Chen S, Correa JD, Wu Y, Albiero ML, Bittinger K, Graves DT. Diabetes enhances IL-17 expression and alters the oral microbiome to increase Its pathogenicity. Cell Host Microbe. 2017;22(120–8):e4.
18.
Zurück zum Zitat Macpherson AJ, Yilmaz B, Limenitakis JP, Ganal-Vonarburg SC. IgA function in relation to the intestinal microbiota. Annu Rev Immunol. 2018;36:359–81.CrossRef Macpherson AJ, Yilmaz B, Limenitakis JP, Ganal-Vonarburg SC. IgA function in relation to the intestinal microbiota. Annu Rev Immunol. 2018;36:359–81.CrossRef
19.
Zurück zum Zitat Bunker JJ, Erickson SA, Flynn TM, Henry C, Koval JC, Meisel M, Jabri B, Antonopoulos DA, Wilson PC, Bendelac A. Natural polyreactive IgA antibodies coat the intestinal microbiota. Science. 2017;358:636.CrossRef Bunker JJ, Erickson SA, Flynn TM, Henry C, Koval JC, Meisel M, Jabri B, Antonopoulos DA, Wilson PC, Bendelac A. Natural polyreactive IgA antibodies coat the intestinal microbiota. Science. 2017;358:636.CrossRef
20.
Zurück zum Zitat Quan CP, Berneman A, Pires R, Avrameas S, Bouvet JP. Natural polyreactive secretory immunoglobulin A autoantibodies as a possible barrier to infection in humans. Infect Immun. 1997;65:3997–4004.CrossRef Quan CP, Berneman A, Pires R, Avrameas S, Bouvet JP. Natural polyreactive secretory immunoglobulin A autoantibodies as a possible barrier to infection in humans. Infect Immun. 1997;65:3997–4004.CrossRef
21.
Zurück zum Zitat Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol. 2011;29:273–93.CrossRef Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol. 2011;29:273–93.CrossRef
22.
Zurück zum Zitat Hapfelmeier S, Lawson MA, Slack E, Kirundi JK, Stoel M, Heikenwalder M, Cahenzli J, Velykoredko Y, Balmer ML, Endt K, Geuking MB, Curtiss R 3rd, McCoy KD, Macpherson AJ. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science. 2010;328:1705–9.CrossRef Hapfelmeier S, Lawson MA, Slack E, Kirundi JK, Stoel M, Heikenwalder M, Cahenzli J, Velykoredko Y, Balmer ML, Endt K, Geuking MB, Curtiss R 3rd, McCoy KD, Macpherson AJ. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science. 2010;328:1705–9.CrossRef
23.
Zurück zum Zitat Macpherson AJ, McCoy KD. Independence Day for IgA. Immunity. 2015;43:416–8.CrossRef Macpherson AJ, McCoy KD. Independence Day for IgA. Immunity. 2015;43:416–8.CrossRef
24.
Zurück zum Zitat Pabst O. New concepts in the generation and functions of IgA. Nat Rev Immunol. 2012;12:821–32.CrossRef Pabst O. New concepts in the generation and functions of IgA. Nat Rev Immunol. 2012;12:821–32.CrossRef
25.
Zurück zum Zitat Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, Ruggiero E, Cho JH, Goodman AL, Flavell RA. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell. 2014;158:1000–10.CrossRef Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, Ruggiero E, Cho JH, Goodman AL, Flavell RA. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell. 2014;158:1000–10.CrossRef
26.
Zurück zum Zitat Pabst O, Slack E. IgA and the intestinal microbiota: the importance of being specific. Mucosal Immunol. 2019;13:12–21.CrossRef Pabst O, Slack E. IgA and the intestinal microbiota: the importance of being specific. Mucosal Immunol. 2019;13:12–21.CrossRef
27.
Zurück zum Zitat Okai S, Usui F, Yokota S, Hori IY, Hasegawa M, Nakamura T, Kurosawa M, Okada S, Yamamoto K, Nishiyama E, Mori H, Yamada T, Kurokawa K, Matsumoto S, Nanno M, Naito T, Watanabe Y, Kato T, Miyauchi E, Ohno H, Shinkura R. High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice. Nat Microbiol. 2016;1:16103.CrossRef Okai S, Usui F, Yokota S, Hori IY, Hasegawa M, Nakamura T, Kurosawa M, Okada S, Yamamoto K, Nishiyama E, Mori H, Yamada T, Kurokawa K, Matsumoto S, Nanno M, Naito T, Watanabe Y, Kato T, Miyauchi E, Ohno H, Shinkura R. High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice. Nat Microbiol. 2016;1:16103.CrossRef
28.
Zurück zum Zitat Catanzaro JR, Strauss JD, Bielecka A, Porto AF, Lobo FM, Urban A, Schofield WB, Palm NW. IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM. Sci Rep. 2019;9:13574.CrossRef Catanzaro JR, Strauss JD, Bielecka A, Porto AF, Lobo FM, Urban A, Schofield WB, Palm NW. IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM. Sci Rep. 2019;9:13574.CrossRef
30.
Zurück zum Zitat Negishi-Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu A, Suda T, Sato K, Takai T, Takayanagi H. Immune complexes regulate bone metabolism through FcRgamma signalling. Nat Commun. 2015;6:6637.CrossRef Negishi-Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu A, Suda T, Sato K, Takai T, Takayanagi H. Immune complexes regulate bone metabolism through FcRgamma signalling. Nat Commun. 2015;6:6637.CrossRef
Metadaten
Titel
Impaired salivary SIgA antibodies elicit oral dysbiosis and subsequent induction of alveolar bone loss
verfasst von
Emily Chang
Ryoki Kobayashi
Kohtaro Fujihashi
Masamichi Komiya
Tomoko Kurita-Ochiai
Publikationsdatum
09.11.2020
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 1/2021
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-020-01418-x

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