請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18922完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 伍安怡 | |
| dc.contributor.author | Chia-Lin Weng | en |
| dc.contributor.author | 翁家琳 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:39:42Z | - |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-21 | |
| dc.identifier.citation | Antachopoulos, C., T.J. Walsh, and E. Roilides. 2007. Fungal infections in primary immunodeficiencies. European journal of pediatrics. 166:1099-1117.
Arai, Y., Y. Nishinaka, T. Arai, M. Morita, K. Mizugishi, S. Adachi, A. Takaori-Kondo, T. Watanabe, and K. Yamashita. 2014. Uric acid induces NADPH oxidase-independent neutrophil extracellular trap formation. Biochemical and biophysical research communications. 443:556-561. Bachiega, T.F., L.A. Dias-Melicio, R.K. Fernandes, H. de Almeida Balderramas, D.R. Rodrigues, V.F. Ximenes, and A.M. de Campos Soares. 2015. Participation of dectin-1 receptor on NETs release against Paracoccidioides brasiliensis: Role on extracellular killing. Immunobiology. Bartneck, M., H.A. Keul, G. Zwadlo-Klarwasser, and J. Groll. 2010. Phagocytosis independent extracellular nanoparticle clearance by human immune cells. Nano Lett. 10:59-63. Berends, E.T., A.R. Horswill, N.M. Haste, M. Monestier, V. Nizet, and M. von Kockritz-Blickwede. 2010. Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps. Journal of innate immunity. 2:576-586. Bianchi, M., M.J. Niemiec, U. Siler, C.F. Urban, and J. Reichenbach. 2011. Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol. 127:1243-1252 e1247. Branzk, N., and V. Papayannopoulos. 2013. Molecular mechanisms regulating NETosis in infection and disease. Semin Immunopathol. 35:513-530. Brinkmann, V., U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann, D.S. Weiss, Y. Weinrauch, and A. Zychlinsky. 2004. Neutrophil extracellular traps kill bacteria. Science (New York, N.Y.). 303:1532-1535. Brinkmann, V., and A. Zychlinsky. 2012. Neutrophil extracellular traps: is immunity the second function of chromatin? J Cell Biol. 198:773-783. Byrd, A.S., X.M. O'Brien, C.M. Johnson, L.M. Lavigne, and J.S. Reichner. 2013. An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans. J Immunol. 190:4136-4148. Cheng, S.C., T. Sprong, L.A. Joosten, J.W. van der Meer, B.J. Kullberg, B. Hube, L. Schejbel, P. Garred, M. van Deuren, and M.G. Netea. 2012. Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs. European journal of immunology. 42:993-1004. Ermert, D., M.J. Niemiec, M. Rohm, A. Glenthoj, N. Borregaard, and C.F. Urban. 2013. Candida albicans escapes from mouse neutrophils. Journal of leukocyte biology. 94:223-236. Ermert, D., C.F. Urban, B. Laube, C. Goosmann, A. Zychlinsky, and V. Brinkmann. 2009. Mouse neutrophil extracellular traps in microbial infections. Journal of innate immunity. 1:181-193. Fuchs, T.A., U. Abed, C. Goosmann, R. Hurwitz, I. Schulze, V. Wahn, Y. Weinrauch, V. Brinkmann, and A. Zychlinsky. 2007. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 176:231-241. Fulurija, A., R.B. Ashman, and J.M. Papadimitriou. 1996. Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance. Microbiology (Reading, England). 142 ( Pt 12):3487-3496. Gazendam, R.P., J.L. van Hamme, A.T. Tool, M. van Houdt, P.J. Verkuijlen, M. Herbst, J.G. Liese, F.L. van de Veerdonk, D. Roos, T.K. van den Berg, and T.W. Kuijpers. 2014. Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects. Blood. 124:590-597. Gow, N.A., F.L. van de Veerdonk, A.J. Brown, and M.G. Netea. 2012. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nature reviews. Microbiology. 10:112-122. Gray, R.D., C.D. Lucas, A. Mackellar, F. Li, K. Hiersemenzel, C. Haslett, D.J. Davidson, and A.G. Rossi. 2013. Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps. Journal of inflammation (London, England). 10:12. Hakkim, A., T.A. Fuchs, N.E. Martinez, S. Hess, H. Prinz, A. Zychlinsky, and H. Waldmann. 2011. Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation. Nature chemical biology. 7:75-77. Horn, D.L., D. Neofytos, E.J. Anaissie, J.A. Fishman, W.J. Steinbach, A.J. Olyaei, K.A. Marr, M.A. Pfaller, C.H. Chang, and K.M. Webster. 2009. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 48:1695-1703. Ifrim, D.C., J.M. Bain, D.M. Reid, M. Oosting, I. Verschueren, N.A. Gow, J.H. van Krieken, G.D. Brown, B.J. Kullberg, L.A. Joosten, J.W. van der Meer, F. Koentgen, L.P. Erwig, J. Quintin, and M.G. Netea. 2014. Role of Dectin-2 for host defense against systemic infection with Candida glabrata. Infect Immun. 82:1064-1073. Jones, F.S. 1927. THE EFFECT OF HEAT ON ANTIBODIES. The Journal of experimental medicine. 46:291-301. Kabir, M.A., M.A. Hussain, and Z. Ahmad. 2012. Candida albicans: A Model Organism for Studying Fungal Pathogens. ISRN Microbiol. 2012:538694. Khandpur, R., C. Carmona-Rivera, A. Vivekanandan-Giri, A. Gizinski, S. Yalavarthi, J.S. Knight, S. Friday, S. Li, R.M. Patel, V. Subramanian, P. Thompson, P. Chen, D.A. Fox, S. Pennathur, and M.J. Kaplan. 2013. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Science translational medicine. 5:178ra140. Kozel, T.R., R.R. Brown, and G.S. Pfrommer. 1987. Activation and binding of C3 by Candida albicans. Infect Immun. 55:1890-1894. Landau, J.W., N. Dabrowa, and V.D. Newcomer. 1965. THE RAPID FORMATION IN SERUM OF FILAMENTS BY CANDIDA ALBICANS. The Journal of investigative dermatology. 44:171-179. Lande, R., D. Ganguly, V. Facchinetti, L. Frasca, C. Conrad, J. Gregorio, S. Meller, G. Chamilos, R. Sebasigari, V. Riccieri, R. Bassett, H. Amuro, S. Fukuhara, T. Ito, Y.J. Liu, and M. Gilliet. 2011. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Science translational medicine. 3:73ra19. Lionakis, M.S., and M.G. Netea. 2013. Candida and host determinants of susceptibility to invasive candidiasis. PLoS Pathog. 9:e1003079. Marr, K.A., S. Arunmozhi Balajee, T.R. Hawn, A. Ozinsky, U. Pham, S. Akira, A. Aderem, and W. Conrad Liles. 2003. Differential Role of MyD88 in Macrophage-Mediated Responses to Opportunistic Fungal Pathogens. Infection and Immunity. 71:5280-5286. Mayer, F.L., D. Wilson, and B. Hube. 2013. Candida albicans pathogenicity mechanisms. Virulence. 4:119-128. McDonald, J.U., M. Rosas, G.D. Brown, S.A. Jones, and P.R. Taylor. 2012. Differential dependencies of monocytes and neutrophils on dectin-1, dectin-2 and complement for the recognition of fungal particles in inflammation. PloS one. 7:e45781. Nani, S., L. Fumagalli, U. Sinha, L. Kamen, P. Scapini, and G. Berton. 2015. Src family kinases and Syk are required for neutrophil extracellular trap formation in response to beta-glucan particles. Journal of innate immunity. 7:59-73. Neeli, I., S.N. Khan, and M. Radic. 2008. Histone Deimination As a Response to Inflammatory Stimuli in Neutrophils. The Journal of Immunology. 180:1895-1902. Netea, M.G., G.D. Brown, B.J. Kullberg, and N.A. Gow. 2008. An integrated model of the recognition of Candida albicans by the innate immune system. Nature reviews. Microbiology. 6:67-78. Netea, M.G., L.A. Joosten, J.W. van der Meer, B.J. Kullberg, and F.L. van de Veerdonk. 2015. Immune defence against Candida fungal infections. Nature reviews. Immunology. 15:630-642. Netea, M.G., C.A. Van Der Graaf, A.G. Vonk, I. Verschueren, J.W. Van Der Meer, and B.J. Kullberg. 2002. The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. The Journal of infectious diseases. 185:1483-1489. Panday, A., M.K. Sahoo, D. Osorio, and S. Batra. 2015. NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cellular & molecular immunology. 12:5-23. Papayannopoulos, V., K.D. Metzler, A. Hakkim, and A. Zychlinsky. 2010. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 191:677-691. Pereira, H.A., and C.S. Hosking. 1984. The role of complement and antibody in opsonization and intracellular killing of Candida albicans. Clinical and experimental immunology. 57:307-314. Pilsczek, F.H., D. Salina, K.K. Poon, C. Fahey, B.G. Yipp, C.D. Sibley, S.M. Robbins, F.H. Green, M.G. Surette, M. Sugai, M.G. Bowden, M. Hussain, K. Zhang, and P. Kubes. 2010. A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol. 185:7413-7425. Remijsen, Q., T. Vanden Berghe, E. Wirawan, B. Asselbergh, E. Parthoens, R. De Rycke, S. Noppen, M. Delforge, J. Willems, and P. Vandenabeele. 2011. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res. 21:290-304. Rohm, M., M.J. Grimm, A.C. D'Auria, N.G. Almyroudis, B.H. Segal, and C.F. Urban. 2014. NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis. Infect Immun. 82:1766-1777. Saijo, S., S. Ikeda, K. Yamabe, S. Kakuta, H. Ishigame, A. Akitsu, N. Fujikado, T. Kusaka, S. Kubo, S.H. Chung, R. Komatsu, N. Miura, Y. Adachi, N. Ohno, K. Shibuya, N. Yamamoto, K. Kawakami, S. Yamasaki, T. Saito, S. Akira, and Y. Iwakura. 2010. Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity. 32:681-691. Soloviev, D.A., S. Jawhara, and W.A. Fonzi. 2011. Regulation of innate immune response to Candida albicans infections by alphaMbeta2-Pra1p interaction. Infect Immun. 79:1546-1558. Soltis, R.D., D. Hasz, M.J. Morris, and I.D. Wilson. 1979. The effect of heat inactivation of serum on aggregation of immunoglobulins. Immunology. 36:37-45. Sonoyama, K., A. Miki, R. Sugita, H. Goto, M. Nakata, and N. Yamaguchi. 2011. Gut colonization by Candida albicans aggravates inflammation in the gut and extra-gut tissues in mice. Medical mycology. 49:237-247. Sur Chowdhury, C., S. Giaglis, U.A. Walker, A. Buser, S. Hahn, and P. Hasler. 2014. Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis research & therapy. 16:R122. Taylor, P.R., S.V. Tsoni, J.A. Willment, K.M. Dennehy, M. Rosas, H. Findon, K. Haynes, C. Steele, M. Botto, S. Gordon, and G.D. Brown. 2007. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nature immunology. 8:31-38. Tsoni, S.V., A.M. Kerrigan, M.J. Marakalala, N. Srinivasan, M. Duffield, P.R. Taylor, M. Botto, C. Steele, and G.D. Brown. 2009. Complement C3 plays an essential role in the control of opportunistic fungal infections. Infect Immun. 77:3679-3685. Urban, C.F., D. Ermert, M. Schmid, U. Abu-Abed, C. Goosmann, W. Nacken, V. Brinkmann, P.R. Jungblut, and A. Zychlinsky. 2009. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog. 5:e1000639. Urban, C.F., U. Reichard, V. Brinkmann, and A. Zychlinsky. 2006. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol. 8:668-676. van Bruggen, R., A. Drewniak, M. Jansen, M. van Houdt, D. Roos, H. Chapel, A.J. Verhoeven, and T.W. Kuijpers. 2009. Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for beta-glucan-bearing particles. Mol Immunol. 47:575-581. Villamón, E., D. Gozalbo, P. Roig, J.E. O’Connor, D. Fradelizi, and M.L. Gil. 2004. Toll-like receptor-2 is essential in murine defenses against Candida albicans infections. Microbes and Infection. 6:1-7. Wang, H., C. Wang, M.H. Zhao, and M. Chen. 2015. Neutrophil extracellular traps can activate alternative complement pathways. Clinical and experimental immunology. 181:518-527. Wang, Y., M. Li, S. Stadler, S. Correll, P. Li, D. Wang, R. Hayama, L. Leonelli, H. Han, S.A. Grigoryev, C.D. Allis, and S.A. Coonrod. 2009. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol. 184:205-213. Yipp, B.G., B. Petri, D. Salina, C.N. Jenne, B.N. Scott, L.D. Zbytnuik, K. Pittman, M. Asaduzzaman, K. Wu, H.C. Meijndert, S.E. Malawista, A. de Boisfleury Chevance, K. Zhang, J. Conly, and P. Kubes. 2012. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med. 18:1386-1393. Zhu, L.L., X.Q. Zhao, C. Jiang, Y. You, X.P. Chen, Y.Y. Jiang, X.M. Jia, and X. Lin. 2013. C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity. 39:324-334. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18922 | - |
| dc.description.abstract | 白色念珠菌是一種雙形真菌，在一般環境下以酵母菌形態存在，當在人類宿主體內，或是處於37度含有血清的環境時會轉變成菌絲形態。對於正常人而言白色念珠菌是一種共生菌，但當宿主免疫不全時他會轉變為病源並導致黏膜或是全身性的念珠菌感染。過去的研究指出慢性肉芽腫以及嗜中性白血球低下症的病人特別容易產生全身性念珠菌感染疾病，顯示嗜中性白血球在抵禦白色念珠菌感染中扮演著重要的角色。Netrophil extracellular traps是由染色質、顆粒蛋白和細胞質蛋白質構成，嗜中性白血球可以借此來清除病源，在過去的研究顯示白色念珠菌可以引起NETs產生，並且可以被NETs清除。
在本篇研究中，我試圖探討opsonized C. albicans和unopsonized C. albicans感染時嗜中性球分別經由什麼機制引起NETs產生。我分別利用opsonized和unopsonized的白色念珠菌刺激野生型以及Ncf-1 KO的嗜中性白血球。實驗結果顯示opsonized C. albicans是經由需要NADPH oxidase活化以及ROS產生的機制引起NETs產生，而unopsonized C. albicans引起的NETs則不需要NADPH oxidase活化。 借由CR3 knockout老鼠實驗，我發現嗜中性球利用CR3辨識opsonized C. albicans並活化PKC、PI3K、Syk的訊息傳遞路徑引起需要ROS的NETs，而unopsonized C. albicans則是借由Dectin-2所辨識並且活化Syk、PKCδ、P38以及ERK的訊息傳遞來引發NETs產生。因此opsonized 和unopsonized 的C. albicans 可以被不同受體辨識並經由不同的路徑引發NETs的產生。 | zh_TW |
| dc.description.abstract | Candida albicans is a dimorphic fungus. It is a commensal in healthy individuals and becomes an opportunistic pathogen in immunocompromised hosts causing mucosal or systemic candidiasis. Previous studies show that, CGD and neutropenia patients are susceptible to systemic candidiasis showing that neutrophil is important to host defense against C. albicans. Neutrophils kill pathogens by neutrophil extracellular traps (NETs), a web like structure composed of chromatins, granular- and cytosolic proteins. Previous studies showed that C. albicans induce NETs via ROS-dependent as well as -independent mechanisms and NETs kill C. albicans.
Here, I investigated the mechanism of NETs formation in response to stimulation by opsonized and unopsonized C. albicans. Neutrophils stimulated with both opsonized and unopsonized C. albicans released NETs. Comparing NETs formation of neutrophils from wild type and Ncf-1 knockout mice in response to opsonized and unopsonized C. albicans, we found that opsonized C. albicans induced-NETs formation was via NADPH oxidase-dependent mechanism but unopsonized C. albicans induced NETs did not require NADPH oxidase mediated-ROS production. Comparing neutrophils from CR3 KO and WT mice, I discovered that neutrophils recognized opsonized C. albicans via CR3. CR3 engagement activated PKC, PI3K, and Syk signaling pathway(s) resulting in NADPH oxidase-dependent NETs production. On the other hand, unopsonized C. albicans is recognized by Dectin-2 and activated Syk, PKCδ, P38 and ERK signaling pathway(s). In conclusion opsonized and unopsonized C. albicans are recognized by different receptor and induce NETs production via different pathways. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:39:42Z (GMT). No. of bitstreams: 1 ntu-105-R03449001-1.pdf: 3856957 bytes, checksum: f050190101bb0658318e6d82026b2bf2 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | Contents
致謝 i 中文摘要 ii Abstract iii Contents v Abbreviations ix Figures Contents x Chapter I. Introduction 2 1. Candida albicans 2 1.1 Candia albicans infection 2 1.2 Neutrophils and Candida albicans 2 1.3 Recognition of Candida albicans by pattern recognition receptor 3 1.4 Opsonization affects immune response to C. albicans 5 2. Neutrophil extracellular traps 6 2.1. NETs morphology and functions 6 2.2. NADPH oxidase dependent NETs production 7 2.3. NADPH oxidase-independent NETs production 8 2.4. Antimicrobial capacity of NETs 9 2.5. NETs production and C. albicans 10 Chapter II. Aims of the study 12 Chapter III. Materials and Methods 14 Part I. Materials 14 1. Mice 14 2. Antibodies 14 3. Inhibitors 15 4. Enzymes 16 5. Solutions 16 6. Chemicals and reagents 18 7. Disposable 20 8. Equipment 21 Part II. Methods 21 1. Isolation of mouse bone marrow neutrophil 21 2. Fungus 22 3. Induction and quantification NET production 22 4. Confocal microscope imaging 23 5. Western blotting 23 6. NETs killing assay 24 7. Statistical analysis 25 Chapter IV. Results 27 1. Both opsonized and unopsonized C. albicans induce NET formation 27 2. Opsonized and unopsonized C. albicans induce NETs through different mechanisms 28 3. C. albicans germination and the presence of complement are both important to NET formation 29 4. Mitochondrial ROS production is not involved in C. albicans-induced NETs production 30 5. Complement receptor 3 (CR3) but not Dectin-1 recognizes opsonized C. albicans and mediates NADPH-oxidase-dependent NETs production 31 6. Dectin-2 recognizes unopsonized C. albicans and mediates NADPH oxidase-independent NETs production 33 7. NET formation induced by C. albicans is independent of TLR4 and Myd88 signaling 33 8. NET formation induced by opsonized C. albicans is through Syk, PKC, PI3K signaling 34 9. Syk, P38, ERK, PKCδ are involved in unopsonized C. albicans-induced NET formation 35 10. NETs is efficient in killing uningested C. albicans 36 11. To examine neutrophil NET formation in response to clinically isolated C.albicans 37 Chapter V. Discussion 39 References 46 Figures 59 | |
| dc.language.iso | en | |
| dc.title | 探討白色念珠菌引起嗜中性白血球產生細胞外網狀結構之機制 | zh_TW |
| dc.title | The Mechanism of Candida albicans-Induced Neutrophil Extracellular Traps Formation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李建國,林錫賢 | |
| dc.subject.keyword | 白色念珠菌,細胞外網狀結構,NADPH氧化?,Dectin-2受體,補體受體3, | zh_TW |
| dc.subject.keyword | Candida albicans,Neutrophil extracellular traps,NADPH oxidase,Dectin-2,Complement receptor 3, | en |
| dc.relation.page | 85 | |
| dc.identifier.doi | 10.6342/NTU201602441 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2016-08-22 | |
| 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 | |
|---|---|---|---|
| ntu-105-1.pdf 目前未授權公開取用 | 3.77 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。