請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76987完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山(Jean-San Chia) | |
| dc.contributor.author | Yu-Hsuan Chu | en |
| dc.contributor.author | 褚昱萱 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:42:33Z | - |
| dc.date.available | 2021-07-10T21:42:33Z | - |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-07-31 | |
| dc.identifier.citation | 1. Hall-Stoodley, L., J.W. Costerton, and P. Stoodley, Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol, 2004. 2(2): p. 95-108.
2. Varma, M.P., et al., Heart failure associated with infective endocarditis. A review of 40 cases. Br Heart J, 1986. 55(2): p. 191-7. 3. Lowy, F.D., Staphylococcus aureus infections. N Engl J Med, 1998. 339(8): p. 520-32. 4. Lucas, V.S., et al., Prevalence, intensity and nature of bacteraemia after toothbrushing. J Dent, 2008. 36(7): p. 481-7. 5. Moreillon, P. and Y.A. Que, Infective endocarditis. Lancet, 2004. 363(9403): p. 139-49. 6. Clarke, J.K., On the bacterial factor in the aetiology of dental caries. Br J Exp Pathol, 1924: p. 5(3): 141–147. 7. Kolaczkowska, E. and P. Kubes, Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol, 2013. 13(3): p. 159-75. 8. Hager, M., J.B. Cowland, and N. Borregaard, Neutrophil granules in health and disease. J Intern Med, 2010. 268(1): p. 25-34. 9. Lacy, P., Mechanisms of degranulation in neutrophils. Allergy Asthma Clin Immunol, 2006. 2(3): p. 98-108. 10. Brinkmann, V., et al., Neutrophil extracellular traps kill bacteria. Science, 2004. 303(5663): p. 1532-5. 11. Fuchs, T.A., et al., Novel cell death program leads to neutrophil extracellular traps. J Cell Biol, 2007. 176(2): p. 231-41. 12. Garcia-Romo, G.S., et al., Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med, 2011. 3(73): p. 73ra20. 13. Khandpur, R., et al., NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med, 2013. 5(178): p. 178ra40. 14. Massberg, B.E.S., Thrombosis as an intravascular effector of innate immunity. Nature Reviews Immunology 2013: p. 34–45. 15. Phillipson, M. and P. Kubes, The neutrophil in vascular inflammation. Nat Med, 2011. 17(11): p. 1381-90. 16. Jung, C.J., et al., Endocarditis pathogen promotes vegetation formation by inducing intravascular neutrophil extracellular traps through activated platelets Circulation, 2015(6): p. 571-81. 17. Cools-Lartigue, J., et al., Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest, 2013. 18. Fuchs, T.A., et al., Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A, 2010. 107(36): p. 15880-5. 19. Metzler, K.D., et al., A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep, 2014. 8(3): p. 883-96. 20. Pilsczek, F.H., et al., A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol, 2010. 185(12): p. 7413-25. 21. Yipp, B.G., et al., Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med, 2012. 18(9): p. 1386-93. 22. Remijsen, Q., et al., Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ, 2011. 18(4): p. 581-8. 23. Hakkim, A., et al., Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation. Nat Chem Biol, 2011. 7(2): p. 75-7. 24. Bianchi, M., et al., Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood, 2009. 114(13): p. 2619-22. 25. Papayannopoulos, V., Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol, 2018. 18(2): p. 134-147. 26. Sollberger, G., D.O. Tilley, and A. Zychlinsky, Neutrophil Extracellular Traps: The Biology of Chromatin Externalization. Dev Cell, 2018. 44(5): p. 542-553. 27. Li, P., et al., PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med, 2010. 207(9): p. 1853-62. 28. Lewis, H.D., et al., Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol, 2015. 11(3): p. 189-91. 29. Konig, M.F. and F. Andrade, A Critical Reappraisal of Neutrophil Extracellular Traps and NETosis Mimics Based on Differential Requirements for Protein Citrullination. Front Immunol, 2016. 7: p. 461. 30. Yang, Z. and D.J. Klionsky, An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol, 2009. 335: p. 1-32. 31. Shrestha, S., J.M. Lee, and C.W. Hong, Autophagy in neutrophils. Korean J Physiol Pharmacol, 2020. 24(1): p. 1-10. 32. Skendros, P., I. Mitroulis, and K. Ritis, Autophagy in Neutrophils: From Granulopoiesis to Neutrophil Extracellular Traps. Front Cell Dev Biol, 2018. 6: p. 109. 33. Remijsen, Q., et al., Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res, 2011. 21(2): p. 290-304. 34. Itakura, A. and O.J. McCarty, Pivotal role for the mTOR pathway in the formation of neutrophil extracellular traps via regulation of autophagy. Am J Physiol Cell Physiol, 2013. 305(3): p. C348-54. 35. McInturff, A.M., et al., Mammalian target of rapamycin regulates neutrophil extracellular trap formation via induction of hypoxia-inducible factor 1 alpha. Blood, 2012. 120(15): p. 3118-25. 36. Germic, N., et al., Neither eosinophils nor neutrophils require ATG5-dependent autophagy for extracellular DNA trap formation. Immunology, 2017. 152(3): p. 517-525. 37. Sil, P., G. Muse, and J. Martinez, A ravenous defense: canonical and non-canonical autophagy in immunity. Curr Opin Immunol, 2018. 50: p. 21-31. 38. Heckmann, B.L. and D.R. Green, LC3-associated phagocytosis at a glance. J Cell Sci, 2019. 132(5). 39. Schille, S., et al., LC3-associated phagocytosis in microbial pathogenesis. Int J Med Microbiol, 2018. 308(1): p. 228-236. 40. Herb, M., A. Gluschko, and M. Schramm, LC3-associated phagocytosis - The highway to hell for phagocytosed microbes. Semin Cell Dev Biol, 2020. 101: p. 68-76. 41. Chia, J.S., et al., Platelet aggregation induced by serotype polysaccharides from Streptococcus mutans. Infect Immun, 2004. 72(5): p. 2605-17. 42. Mustard, J.F., et al., Preparation of suspensions of washed platelets from humans. Br J Haematol, 1972. 22(2): p. 193-204. 43. Lood, C., et al., Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med, 2016. 22(2): p. 146-53. 44. Huang, J., et al., Activation of antibacterial autophagy by NADPH oxidases. Proc Natl Acad Sci U S A, 2009. 106(15): p. 6226-31. 45. Martinez, J., et al., Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol, 2015. 17(7): p. 893-906. 46. Matsunaga, K., et al., Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol, 2009. 11(4): p. 385-96. 47. Boyle, K.B. and F. Randow, Rubicon swaps autophagy for LAP. Nat Cell Biol, 2015. 17(7): p. 843-5. 48. Bidani, A., et al., Bactericidal activity of alveolar macrophages is suppressed by V-ATPase inhibition. Lung, 2000. 178(2): p. 91-104. 49. Hsu, C.C., et al., Neutrophil Extracellular Traps Enhance Staphylococcus Aureus Vegetation Formation through Interaction with Platelets in Infective Endocarditis. Thromb Haemost, 2019. 119(5): p. 786-796. 50. Darrah, E., et al., Peptidylarginine deiminase 2, 3 and 4 have distinct specificities against cellular substrates: novel insights into autoantigen selection in rheumatoid arthritis. Ann Rheum Dis, 2012. 71(1): p. 92-8. 51. Spengler, J., et al., Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid. Arthritis Rheumatol, 2015. 67(12): p. 3135-45. 52. Ouseph, M.M., et al., Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis. Blood, 2015. 126(10): p. 1224-33. 53. Clancy, L., et al., The role of RNA uptake in platelet heterogeneity. Thromb Haemost, 2017. 117(5): p. 948-961. 54. Branzk, N., et al., Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat Immunol, 2014. 15(11): p. 1017-25. 55. Shun, C.T., et al., Glucosyltransferases of viridans streptococci are modulins of interleukin-6 induction in infective endocarditis. Infect Immun, 2005. 73(6): p. 3261-70. 56. Dorner, T., Therapy: Hydroxychloroquine in SLE: old drug, new perspectives. Nat Rev Rheumatol, 2010. 6(1): p. 10-1. 57. Yuan, N., et al., Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica, 2015. 100(3): p. 345-56. 58. Yan, Y., et al., Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways. Sci Rep, 2016. 6: p. 37052. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76987 | - |
| dc.description.abstract | 嗜中性白血球作為先天免疫上第一線的防禦來抵禦感染，目前提出有三種嗜中性白血球的機制可以抑制病原菌的擴散，包括吞噬作用、去顆粒作用以及形成嗜中性白血球胞外陷阱(Neutrophil extracellular traps，NETs)。NETs被認為可以防止細菌與真菌的擴散，然而，在一些調控異常的情況下，它們也會影響疾病的惡化，例如自體免疫疾病以及癌症。我們先前的研究證明了NETs在感染性心內膜炎(Infective Endocarditis，IE)的病理機轉中扮演重要角色，同時也顯示IE的致病菌-轉糖鏈球菌(Streptococcus mutans)不僅可以直接誘導嗜中性白血球組蛋白瓜氨酸化，也會提升血小板上P-selectin的表現量，進而提供另一個訊號來促進NETosis發生。在本篇研究中，我們發現轉糖鏈球菌誘導的NETosis需要依靠嗜中性白血球彈性蛋白酶的活性，而不需要PAD4介導的組蛋白瓜氨酸化。此外，在沒有血小板的條件下，轉糖鏈球菌的感染會誘導嗜中性白血球LC3B-II表現，而經由bafilomycin A1這個液胞H+-ATPase抑制劑的處理之下，則會阻止轉糖鏈球菌誘導的LC3B-II表現，並促進組蛋白瓜氨酸化、彈性蛋白酶易位以及NET形成。在共軛焦顯微鏡的圖像中顯示Rubicon與LC3B具有共定位，意味著在轉糖鏈球菌的感染下，會誘導LC3相關吞噬作用(LC3-associated phagocytosis，LAP)的形成。在bafilomycin A1的處理之下，會降低嗜中性白血球吞噬殺死轉糖鏈球菌的能力，證實LAP在嗜中性白血球對抗轉糖鏈球菌感染中的重要性。綜合來說，這些研究結果顯示當利用bafilomycin A1抑制轉糖鏈球菌誘導的LAP形成，將會促進組蛋白瓜氨酸化、彈性蛋白酶易位以及NET形成。 | zh_TW |
| dc.description.abstract | Neutrophils are the first line of innate immune defense against infection. Three mechanisms of neutrophils to restrain pathogen spreading are proposed: phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). NETs are thought to prevent bacterial and fungal dissemination; however, in some unregulated condition, they also play roles in disease progression, such as autoimmune diseases and tumor. Our previous study demonstrated the important role of NETs in the pathogenesis of infective endocarditis (IE) and showed that Streptococcus mutans (S. mutans), an IE-pathogen, not only directly induced neutrophil histone citrullination, but also up-regulated the expression of P-selectin on platelets to provide another signal to promote the NETosis. In this study, we found S. mutans-induced NETosis relied on neutrophil elastase activity and was independent of PAD4-mediated histone citrullination. In addition, S. mutans infection induced LC3B-II expression in neutrophils, and treatment with bafilomycin A1, a vacuolar H+-ATPase inhibitor, blocked S. mutans-induced LC3B-II expression, and promoted histone citrullination, elastase translocation and NET formation in the absence of platelets. Confocal microscopy image showed the colocalization of Rubicon and LC3B, suggesting S. mutans infection induced the formation of the LC3-associated phagocytosis (LAP). Treatment with bafilomycin A1 reduced neutrophil phagocytic killing activity against S. mutans, confirmed the role of LAP in neutrophil against S. mutans infection. Taken together, these data suggested inhibition of S. mutans-induced LAP formation by bafilomycin A1 will promote neutrophil histone citrullination, elastase translocation and NET formation. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:42:33Z (GMT). No. of bitstreams: 1 U0001-2907202012015900.pdf: 3355823 bytes, checksum: 8d058f8c14bbc6d94d403b4158e63ad5 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝 i 摘要 ii ABSTRACT iii Contents v List of Figures viii Chapter 1 Introduction 1 1.1 Infective Endocarditis 1 1.2 Streptococcus mutans 2 1.3 Neutrophils 2 1.3.1 Neutrophil extracellular traps 3 1.3.2 Mechanisms of neutrophil extracellular traps formation 4 1.4 Autophagy 6 1.4.1 Autophagy and NET formation 7 1.4.2 The relationship between autophagy and phagocytosis 7 Chapter 2 Purpose and Aims 9 Chapter 3 Materials and Methods 11 3.1 Bacterial strains and Growth conditions 11 3.2 Preparation of Platelets and Neutrophils 11 3.3 Induction of NET formation 13 3.4 Immunofluorescence Visualization of NETs 13 3.5 Western Blotting 15 3.6 P-Selectin Expression of Platelets 16 3.7 Bactericidal and Phagocytosis assays 16 Chapter 4 Results 18 4.1 S. mutans induces platelet-independent NETosis in specific plasma obtained from some specific healthy donors 18 4.2 S. mutans-induced NETosis can be inhibited by cytochalasin D, GSK484, bafilomycin A1 and 3-methyladenine in the presence of platelets 18 4.3 The platelet-dependent S. mutans-induced NETosis is autophagy-dependent and does not require PAD4-mediated histone citrullination 20 4.4 The platelet-dependent S. mutans-induced NETosis relies on neutrophil elastase activity 21 4.5 Neutrophils stimulation with rapamycin or S. mutans enhance LC3B-II accumulation but does not trigger NETosis 22 4.6 Bafilomycin A1 promotes S. mutans-induced NETosis 23 4.7 Autophagy inhibitors have different influence in S. mutans-stimulated neutrophils 24 4.8 S. mutans infection induces LC3-associated phagocytosis 26 4.9 Bafilomycin A1 inhibits neutrophil bactericidal activity 28 Chapter 5 Discussion 29 5.1 S. mutans induces platelet-independent NETosis in specific plasma 29 5.2 The platelet-dependent S. mutans-induced NETosis mechanisms 30 5.3 S. mutans infection induces LC3-associated phagocytosis 32 Reference 35 Figures 43 | |
| dc.language.iso | en | |
| dc.subject | 感染性心內膜炎 | zh_TW |
| dc.subject | 嗜中性白血球胞外陷阱 | zh_TW |
| dc.subject | 轉糖鏈球菌 | zh_TW |
| dc.subject | 血小板 | zh_TW |
| dc.subject | LC3相關吞噬作用 | zh_TW |
| dc.subject | infective endocarditis | en |
| dc.subject | platelets | en |
| dc.subject | LC3-associated phagocytosis | en |
| dc.subject | Streptococcus mutans | en |
| dc.subject | neutrophil extracellular traps | en |
| dc.title | 探討感染性心內膜炎中轉糖鏈球菌誘導嗜中性白血球胞外網狀結構形成機制 | zh_TW |
| dc.title | Mechanisms of Neutrophil Extracellular Traps Formation Induced by Streptococcus mutans in Infective Endocarditis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.advisor-orcid | 賈景山(0000-0002-5431-0712) | |
| dc.contributor.coadvisor | 鍾筱菁(Chiau-Jing Jung) | |
| dc.contributor.oralexamcommittee | 黃偉邦(Wei-Pang Huang),詹智強(Chih-Chiang Chan) | |
| dc.subject.keyword | 嗜中性白血球胞外陷阱,感染性心內膜炎,轉糖鏈球菌,血小板,LC3相關吞噬作用, | zh_TW |
| dc.subject.keyword | neutrophil extracellular traps,infective endocarditis,Streptococcus mutans,platelets,LC3-associated phagocytosis, | en |
| dc.relation.page | 65 | |
| dc.identifier.doi | 10.6342/NTU202002027 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-07-31 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2907202012015900.pdf 未授權公開取用 | 3.28 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。