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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山(Jean-San Chia) | |
| dc.contributor.author | Nian-Ping Hsieh | en |
| dc.contributor.author | 謝念平 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:53:46Z | - |
| dc.date.available | 2021-07-10T21:53:46Z | - |
| dc.date.copyright | 2019-08-29 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-13 | |
| dc.identifier.citation | 1. Bojalil, R., et al., Frequency and clinical significance of a variety of autoantibodies in patients with definite infective endocarditis. J Clin Rheumatol, 2012. 18(2): p. 67-70.
2. Gilkeson, G.S., et al., Induction of anti-double stranded DNA antibodies in normal mice by immunization with bacterial DNA. (0022-1767 (Print)). 3. Gilkeson, G.S., A.M. Pippen, and D.S. Pisetsky, Induction of cross-reactive anti-dsDNA antibodies in preautoimmune NZB/NZW mice by immunization with bacterial DNA. J Clin Invest, 1995. 95(3): p. 1398-402. 4. Bluestone, J.A., G. Herold K Fau - Eisenbarth, and G. Eisenbarth, Genetics, pathogenesis and clinical interventions in type 1 diabetes. (1476-4687 (Electronic)). 5. Ercolini, A.M. and S.D. Miller, The role of infections in autoimmune disease. Clinical and experimental immunology, 2009. 155(1): p. 1-15. 6. Adderson, E.E., et al., Molecular analysis of polyreactive monoclonal antibodies from rheumatic carditis: human anti-N-acetylglucosamine/anti-myosin antibody V region genes. (0022-1767 (Print)). 7. van den Berg, B., et al., Guillain-Barre syndrome: pathogenesis, diagnosis, treatment and prognosis. (1759-4766 (Electronic)). 8. Gallo, P.M., et al., Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity. Immunity, 2015. 42(6): p. 1171-84. 9. Shlomchik, M.J., M.J. Craft Je Fau - Mamula, and M.J. Mamula, From T to B and back again: positive feedback in systemic autoimmune disease. (1474-1733 (Print)). 10. Desai, D.D. and T.N. Marion, Induction of anti-DNA antibody with DNA-peptide complexes. (0953-8178 (Print)). 11. Lande, R., et al., Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. (1946-6242 (Electronic)). 12. Han, S., et al., Mechanisms of autoantibody production in systemic lupus erythematosus. Frontiers in immunology, 2015. 6: p. 228-228. 13. Toong, C., S. Adelstein, and T.G. Phan, Clearing the complexity: immune complexes and their treatment in lupus nephritis. International journal of nephrology and renovascular disease, 2011. 4: p. 17-28. 14. Fu, S.M., et al., Anti-dsDNA Antibodies are one of the many autoantibodies in systemic lupus erythematosus. (2046-1402 (Print)). 15. Krzysciak, W., et al., The virulence of Streptococcus mutans and the ability to form biofilms. (1435-4373 (Electronic)). 16. Welin-Neilands, J. and G. Svensäter, Acid tolerance of biofilm cells of Streptococcus mutans. Applied and environmental microbiology, 2007. 73(17): p. 5633-5638. 17. Bowen, W.H. and H. Koo, Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. (1421-976X (Electronic)). 18. Hamada S Fau - Koga, T., T. Koga T Fau - Ooshima, and T. Ooshima, Virulence factors of Streptococcus mutans and dental caries prevention. (0022-0345 (Print)). 19. Al-Senaidi, K.S., A.-A.A. Abdelmogheth, and A.A. Balkhair, Complicated subacute bacterial endocarditis in a patient with ventricular septal defect. Sultan Qaboos University medical journal, 2014. 14(1): p. e130-e133. 20. Mylonakis, E. and S.B. Calderwood, Infective endocarditis in adults. (0028-4793 (Print)). 21. Fujiwara, T., et al., Deletion and reintroduction of glucosyltransferase genes of Streptococcus mutans and role of their gene products in sucrose dependent cellular adherence. (0882-4010 (Print)). 22. Shiroza T Fau - Ueda, S., H.K. Ueda S Fau - Kuramitsu, and H.K. Kuramitsu, Sequence analysis of the gtfB gene from Streptococcus mutans. (0021-9193 (Print)). 23. Banas, J.A. and M.M. Vickerman, Glucan-binding proteins of the oral streptococci. (1544-1113 (Electronic)). 24. Hannig, C., et al., Electron microscopic detection and activity of glucosyltransferase B, C, and D in the in situ formed pellicle. (1879-1506 (Electronic)). 25. Nakano, Y.J. and H.K. Kuramitsu, Mechanism of Streptococcus mutans glucosyltransferases: hybrid-enzyme analysis. Journal of bacteriology, 1992. 174(17): p. 5639-5646. 26. Bleiziffer, I., et al., The Plasmin-Sensitive Protein Pls in Methicillin-Resistant Staphylococcus aureus (MRSA) Is a Glycoprotein. PLoS pathogens, 2017. 13(1): p. e1006110-e1006110. 27. Chia, J.S., et al., Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus mutans in humans. Infection and immunity, 1997. 65(3): p. 1126-1130. 28. Smith, D.J. and M.A. Taubman, Effect of local deposition of antigen on salivary immune responses and reaccumulation of mutans streptococci. (0271-9142 (Print)). 29. Smith Dj Fau - Taubman, M.A., J.L. Taubman Ma Fau - Ebersole, and J.L. Ebersole, Local and systemic antibody response to oral administration of glucosyltransferase antigen complex. (0019-9567 (Print)). 30. Chia, J.S., et al., Human T-cell responses to the glucosyltransferases of Streptococcus mutans. Clinical and diagnostic laboratory immunology, 2001. 8(2): p. 441-445. 31. Martin, F. and J.F. Kearney, B-cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a 'natural immune memory'. (0105-2896 (Print)). 32. Martin, F., A.M. Oliver, and J.F. Kearney, Marginal Zone and B1 B Cells Unite in the Early Response against T-Independent Blood-Borne Particulate Antigens. Immunity, 2001. 14(5): p. 617-629. 33. Allman, D. and S. Pillai, Peripheral B cell subsets. (0952-7915 (Print)). 34. Zandvoort, A. and W. Timens, The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens. Clinical and experimental immunology, 2002. 130(1): p. 4-11. 35. Cerutti, A., I. Cols M Fau - Puga, and I. Puga, Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. (1474-1741 (Electronic)). 36. Pillai, S. and A. Cariappa, The follicular versus marginal zone B lymphocyte cell fate decision. (1474-1741 (Electronic)). 37. Lopes-Carvalho, T., J. Foote, and J.F. Kearney, Marginal zone B cells in lymphocyte activation and regulation. Current opinion in immunology, 2005. 17(3): p. 244-250. 38. Bendelac, A., J.F. Bonneville M Fau - Kearney, and J.F. Kearney, Autoreactivity by design: innate B and T lymphocytes. (1474-1733 (Print)). 39. Martin, F. and J.F. Kearney, Marginal-zone B cells. (1474-1733 (Print)). 40. Park, C., et al., Positive selection of type II collagen-reactive CD80(high) marginal zone B cells in DBA/1 mice. (1521-7035 (Electronic)). 41. Romero-Ramirez, S., et al., Innate-like B cell subsets during immune responses: Beyond antibody production. (1938-3673 (Electronic)). 42. Hoffman, W., F.G. Lakkis, and G. Chalasani, B Cells, Antibodies, and More. (1555-905X (Electronic)). 43. Yam-Puc, J.C., et al., Role of B-cell receptors for B-cell development and antigen-induced differentiation. F1000Research, 2018. 7: p. 429-429. 44. Do, R.K., et al., Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response. (0022-1007 (Print)). 45. Colino, J., C.M. Shen Y Fau - Snapper, and C.M. Snapper, Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms. (0022-1007 (Print)). 46. Gaynor, B., et al., Peptide inhibition of glomerular deposition of an anti-DNA antibody. (0027-8424 (Print)). 47. Sun, Y., et al., Peptide mimicking antigenic and immunogenic epitope of double-stranded DNA in systemic lupus erythematosus. (0953-8178 (Print)). 48. Dai, H. and X.M. Gao, Elevated levels of serum antibodies against alpha-1, 6-glucan in patients with systemic lupus erythematosus or rheumatoid arthritis. (1674-8018 (Electronic)). 49. Dai, H., et al., Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus. (1477-0962 (Electronic)). 50. Willison, H.J. and C.S. Goodyear, Glycolipid antigens and autoantibodies in autoimmune neuropathies. (1471-4981 (Electronic)). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77275 | - |
| dc.description.abstract | 目前已知感染可能導致宿主產生自體免疫抗體並促進自體免疫疾病的發生。我們先前的研究發現若將人類口腔中常見的轉糖鏈球菌(Streptococcus mutans)從尾靜脈施打感染老鼠，則老鼠會產生抗雙股去氧核醣核酸抗體(anti-dsDNA antibody)。轉糖鏈球菌的表面蛋白葡糖基轉移酶B(glucosyltransferase B, GtfB)可透過刺激緣區B細胞 (marginal zone B)產生抗雙股去氧核醣核酸抗體。關於其中的詳細機制仍尚未研究透徹。在本篇研究中，我們發現由尾靜脈施打入葡糖基轉移酶C亦可同施打葡糖基轉移酶B般誘發BALB/c小鼠產生抗雙股去氧核醣核酸抗體。對老鼠施打缺乏各種葡糖基轉移酶的轉糖鏈球菌NHS1DD則無法誘導抗雙股去氧核醣核酸抗體產生，說明葡糖基轉移酶對誘發抗雙股去氧核醣核酸抗體產生相當重要。為確認哪一片段的葡糖基轉移酶B負責誘發抗雙股去氧核醣核酸抗體產生，我們生產並大量表現葡糖基轉移酶B的氨基端與羧基端及葡糖基轉移酶C的氨基端片段。實驗結果發現僅有葡糖基轉移酶B的氨基端可在活體中誘發抗雙股去氧核醣核酸抗體產生，並活化邊緣區B細胞以及濾泡B細胞(follicular B cell)使之生產抗雙股去氧核醣核酸抗體。專一性抗雙股去氧核醣核酸的抗體無法辨識葡糖基轉移酶B的氨基端，且葡糖基轉移酶B的氨基端上並無偵測到醣類成分，說明葡糖基轉移酶B的氨基端並未含有雙股去氧核醣核酸及醣類分子。總結而言，葡糖基轉移酶B的氨基端在轉糖鏈球菌感染引起的菌血症中扮演誘導抗雙股去氧核醣核酸抗體產生的重要角色，並可能進一步誘導自體抗體的產生與自體免疫疾病的發
生。 | zh_TW |
| dc.description.abstract | Infections may contribute to the development of autoantibodies production and the progression of autoimmune diseases. Our previous data showed that bacteremia caused by Streptococcus mutans, an oral commensal, induces autoantibody production in a murine model. The recombinant protein of glucosyltransferase B (GtfB), a surface protein of S.mutans, induces anti-dsDNA IgG production in the MZ B cells-dependent manner. The detailed mechanism remains unclear. Here, we demonstrated that intravascular injection of another glucosyltransferase, GtfC, also induces anti-dsDNA antibodies production in BALB/c mice. An isogenic strain deficient in Gtfs (NHS1DD) failed to induce anti-dsDNA antibody production, confirming the role of Gtfs. To identify which part of GtfB is responsible for antibody production, the recombinant proteins of N-terminal and C-terminal domain of GtfB and the N-terminal domain of GtfC were generated. N-terminal domain of GtfB, not N-terminal domain of GtfC and C-terminal domain of GtfB, induced anti-dsDNA antibodies production in vivo and activated MZ B cells and FO B cells to produce anti-dsDNA antibodies. The specific anti-dsDNA antibody cannot recognize the N-terminal domain of GtfB and no sugar component can be detected in N-terminal domain of GtfB, suggesting that N-terminal domain of GtfB did not contain dsDNA and sugar moieties. Taken together, the N-terminal domain of GtfB is, at least partially, responsible for induce the anti-dsDNA antibody production in S. mutans-induced bacteremia, which may contribute to autoantibody production in patients with autoimmune diseases. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:53:46Z (GMT). No. of bitstreams: 1 ntu-108-R06449002-1.pdf: 3513825 bytes, checksum: 401e7ff3db968bbdc491fd000bcbd65e (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 致謝………………………………………………………………………………………I
Abstract………………………………………………………………………………….II 中文摘要……………………………………………………………………………….III Contents…………………………………………………………………………...……IV 表目錄…………………………………………………………………………………..V 圖目錄…………………………………………………………………………….……VI Chapter 1. Introduction 1 1.1 The relationship between infection and autoantibody production 1 1.2 Anti-dsDNA antibodies 2 1.3 Streptococcus mutans (S. mutans) 2 1.4 Glucosyltransferase (Gtf) 3 1.5 Marginal zone B cell (MZ B) 4 1.6 Follicular B cell (FO B) 6 Chapter 2. Purpose and Specific Aim 8 Chapter 3. Materials and methods 9 3.1 Animals 9 3.2 Construction of recombinant protein expressing plasmids 9 3.3 Bacterial strains and growth conditions 10 3.4 Recombinant protein expression and purification 11 3.5 Extraction of S. mutans genomic DNA 12 3.6 Enzyme-linked immunosorbent assay (ELISA) 12 3.7 Western blotting (WB) 14 3.8 Ex vivo stimulation of MZ B and FO B cells 15 3.9 Detection of DNA-like configuration on recombinant proteins 16 3.10 Glycoprotein staining 16 3.11 DNA-binding activity assay 17 3.12 Statistical analysis 18 Chapter 4. Results 19 4.1 GtfB and GtfC recombinant proteins could induce anti-dsDNA IgG production in mouse model 19 4.2 Gtfs play a critical role in induction of anti-dsDNA antibodies in mouse model 19 4.3 Induction of anti-dsDNA antibodies by truncated form of GtfB and GtfC in mouse model 20 4.4 Ex vivo stimulation of MZ B and FO B cells by S.mutans recombinant proteins 21 4.5 The role of DNA-binding in induction of anti-dsDNA antibodies 22 4.6 Detection of DNA-like configuration on GtfB, GtfC and GtfB N-terminal domain 23 Chapter 5. Discussion 25 5.1 Mechanism of anti-dsDNA antibodies production induced by GtfB, GtfC and GtfB N-terminal recombinant proteins in murine model 25 5.2 Induction of anti-dsDNA antibodies by T-dependent and/or T-independent pathway 28 Chapter 6. References 29 Chapter 7. Table 34 Chapter 8. Figures 35 Chapter 9. Supplementary figures 54 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討血液循環系統中轉糖鏈球菌之葡糖基轉移酶引發抗雙股去氧核糖核酸抗體生成之機制 | zh_TW |
| dc.title | Mechanism of Anti-dsDNA Antibody Production Induced by Circulating Streptococcus mutans Glucosyltransferases | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鍾筱菁(Chiau-Jing Jung),李建國(Chien-Kuo Lee) | |
| dc.subject.keyword | 轉糖鏈球菌,葡糖基轉移?,抗雙股去氧核醣核酸抗體,邊緣區 B 細胞,濾泡 B 細胞, | zh_TW |
| dc.subject.keyword | Streptococcus mutans,glucosyltransferase,anti-dsDNA antibody,marginal zone B cell,follicular B cell, | en |
| dc.relation.page | 55 | |
| dc.identifier.doi | 10.6342/NTU201903044 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2019-08-13 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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