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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 孔祥智(John T. Kung) | |
| dc.contributor.author | Chen-Cheng Lee | en |
| dc.contributor.author | 李振誠 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:39:44Z | - |
| dc.date.available | 2016-03-04 | |
| dc.date.copyright | 2013-03-04 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-09-11 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63406 | - |
| dc.description.abstract | 後天免疫系統缺乏之 Rag-1 剔除小鼠對於單核球增生性李斯特菌感染具有極高
之耐受性。為了進一步暸解淋巴球在此一特殊現象中扮演的角色，本文利用缺少單一淋巴球系之基因剔除小鼠研究此一現象。相對於缺乏 T 淋巴球系之小鼠，缺乏 B 淋巴球之小鼠感染李斯特菌後呈現較低的細菌數與較高的存活率。其趨勢與Rag-1 剔除小鼠相似。接受邊緣區 B 細胞移植之 Rag-1 剔除小鼠與第十型介白素剔除小鼠具有較高之第十型介白素以及李斯特菌數， 並且γ-干擾素呈現下降的現象；反之接受濾泡性 B 細胞移植之小鼠則無上述現像。另外，第十型介白素抗體能夠中和此一邊緣區 B 細胞依賴型之現象。本文亦利用邊緣區 B 細胞缺乏之B 細胞專一型 Rbpj 剔除小鼠，研究邊緣區 B 細胞對李斯特菌感染所造成之影響。李斯特菌感染之邊緣區 B 細胞缺乏之基因剔除小鼠，呈現與 B 細胞缺乏之小鼠相似之現象，包含較低的李斯特菌數以及更高的存活率。有鑒於已知許多型細胞能夠產生第十型介白素，本文在此更進一步指出邊緣區 B 細胞才是李斯特菌感染時主要產生第十型介白素之細胞，並且造成宿主對於李斯特菌之感受性上升。一般認為，邊緣區 B 細胞在感染疾病中是扮演保護者之角色﹔邊緣區 B 細胞提高宿主對李斯特菌感受性之現象反而與此一觀念大相庭逕。本文提出強力證據，證明邊緣區 B 細胞在李斯特菌感染中扮演不利宿主的角色，此一現象很可能亦發生於其他類型之感染疾病。邊緣區 B 細胞對於其他類型之感染症所扮演之角色，則尚須進一步之研究。 | zh_TW |
| dc.description.abstract | Rag-1-KO mice are highly resistant to Listeria monocytogenes infection. The role played by the many Rag-1-dependent lymphocyte lineages was studied using a genetic approach in which each Rag-1-dependent lymphocyte lineage was eliminated one at a time. Only B cell-deficient Igh-KO mice displayed reduced bacterial load and improved survival upon Listeria infection. Listeria infection of Rag-1-KO and Il-10-KO hosts that had been adoptively transferred with marginal zone B cells, but not follicular B cells, resulted in heightened bacterial load which was accompanied by increased Il-10 and reduced Ifn-γ production. This marginal zone B cell-dependent increase in bacterial load was eliminated by anti-Il-10 mAb. In addition, Listeria infection of marginal zone B cell-deficient Rbpj-cKO mice showed decreased bacterial load and increased survival. Whereas multiple cell types have been shown to be capable of Il-10 production, our results show that the marginal B cell is the most dominant and relevant Il-10 source in the context of Listeria susceptibility. In marked contrast to the generally protective nature of marginal zone B cells in defending against pathogenic infection, our results demonstrate a detrimental role they play in Listeria infection and possibly other infections also. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:39:44Z (GMT). No. of bitstreams: 1 ntu-101-D95449002-1.pdf: 2356891 bytes, checksum: 899d3003e275fce7b2af4ef36fd161bf (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Table of Contents
Thesis Defense Committee Examination Report …………………………………… i Acknowledgement ……………………………………………………………………. ii Abstract (Chinese) …………………………………………………………………... iv Abstract ………………………………………………………………………………. v Abbreviation ……………………………………………………………………….... vii Table of Contents …………………………………………………………………… viii List of Figures ………………………………………………………………………. xiv Chapter I. Introduction …………………………………………………………….. 1 1.1 Listeria monocytogenes (Lm) ………………………………………………… 2 1.2 Detrimental roles of lymphocytes in Lm infection …………………………… 4 1.3 Innate immune responses against Lm infection ………………………………. 5 1.4 Innate immune responses favored Lm infection ………………………………. 6 1.5 Protective roles of marginal zone B cells in infectious diseases ………………. 7 1.6 Role of MZB cells in systemic Lm infection: As resistance or susceptibility factors? ………………………………………………………………………… 8 Chapter II Materials and Methods ………………………………………………… 10 Part 1 Materials ………………………………………………………………….. 11 2.1.1 Mice ……………………………………………………………………… 11 2.1.2 Antibodies ……………………………………………………………….. 12 2.1.3 Primers …………………………………………………………………… 13 2.1.4 Reagents …………………………………………………………………. 14 2.1.5 Equipments………………………………………………………………. 16 Part 2 Methods …………………………………………………………………… 18 2.2.1 Genotyping of MZB-deficient mice ……………………………………... 18 2.2.2 Listeria infection ………………………………………………………… 18 2.2.3 Preparation of live and heat-killed (HK) Lm …………………………..... 19 2.2.4 Complement-mediated depletion of T cells ……………………………... 20 2.2.5 Sorting of non-B/T, FOB and MZB cells ……………………………….. 20 2.2.6 Il-10 induction in vitro and measurements …………………………….... 21 2.2.7 Tissue cytokine measurements …………………………………………... 22 2.2.8 Il-10 neutralization in vivo ………………………………………………. 22 2.2.9 Determination of spleen and liver CFU …………………………………. 23 2.2.10 Histological immunofluorescent analysis …………………………….... 23 2.2.11 Statistical analysis …………………………………………………….... 25 Chapter III Results ………………………………………………………………….. 26 3.1 T cells are not susceptibility factors in Lm infection ………………………….. 27 3.2 B cell-deficient mice display increased resistance to Lm infection ………….... 27 3.3 Il-10 production correlates with increase of host susceptibility to Lm infection ……………………………………………………………………….. 28 3.4 Lm-infected Igh-KO mice show decreased Il-10 production …………………. 30 3.5 MZB cells are major Il-10 producing cells in responding to Lm stimulation .... 31 3.6 MZ, but not FO, B cells regulate innate immune responses that restrain Lm infection ……………………………………………………………………….. 33 3.7 Il-10 is necessary for MZB cells regulating innate immunity battling with Lm infection ……………………………………………………………………….. 35 3.8 MZB cells inhibit innate immunity against Lm through Il-10 production ……. 36 3.9 MZB cell-deficient Rbpj-cKO mice display increased resistance to Lm infection ……………………………………………………………………….. 38 3.10 Missing of MZB cell is responsible for increased resistance on Rbpj-cKO mice …………………………………………………………………………. 39 3.11 Lm trapping by spleen is unaltered in the Rbpj-cKO mice ………………….. 39 3.12 Increased Lm resistance in Rbpj-cKO mice is correlated with reduced Il-10 but not Ifn-α production ………………………………………………………… 41 3.13 Il-10 neutralization further reduces bacterial load in Lm-infected Ifnar-KO mice …………………………………………………………………………. 42 3.14 Migration of DCs Lm induced into PALS is unaltered in the Rbpj-cKO and Il-10-KO mice ………………………………………………………………. 43 3.15 Development of Tip-DC requires MZB cells and Il-10 …………………….. 44 Chapter IV Discussion ……………………………………………………………… 46 4.1 MZB cells are a major Il-10 source relevant to host susceptibility on Lm infection ………………………………………………………………………. 47 4.2 Detrimental effects of Il-10 of MZB cell on Lm infection is independent of Ifnar signaling ………………………………………………………………………. 49 4.3 Not yet defined regulations Il-10 possessed in Lm infection …………………. 51 4.4 Tissue specific innate immune responses induced by Lm infection …………... 53 4.5 Detrimental role of MZ B cells: Is it applicable to infectious agents except Lm? …………………………………………………………………………..... 55 4.6 Model: Marginal zone B cells play as a detrimental first line defense in Lm infection ……………………………………………………………………….. 57 References ………………………………………………………………………….... 59 Figures ……………………………………………………………………………….. 71 Appendix ……………………………………………………………………………... 98 | |
| dc.language.iso | en | |
| dc.subject | γ-干擾素 | zh_TW |
| dc.subject | Rag-1 剔除小鼠 | zh_TW |
| dc.subject | 邊緣區 B 細胞 | zh_TW |
| dc.subject | 單核球增生性李斯特菌 | zh_TW |
| dc.subject | 第十型介白 素 | zh_TW |
| dc.subject | interferon-γ | en |
| dc.subject | Rag-1-KO | en |
| dc.subject | Listeria monocytogenes | en |
| dc.subject | interleukin-10 | en |
| dc.subject | marginal zone B cells | en |
| dc.title | 邊緣區B細胞為單核球增多性李斯特菌感受性之主要介白素10來源 | zh_TW |
| dc.title | Marginal zone B cell is a major source of Il-10 in Listeria monocytogenes susceptibility | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 果伽蘭(Chia-Lam Kuo),顧家?(Chia-Chi Ku),繆希椿(Shi-Chuen Miaw),伍安怡(Betty Wu-Hsieh) | |
| dc.subject.keyword | Rag-1 剔除小鼠,邊緣區 B 細胞,單核球增生性李斯特菌,第十型介白 素,γ-干擾素, | zh_TW |
| dc.subject.keyword | Rag-1-KO,marginal zone B cells,Listeria monocytogenes,interleukin-10,interferon-γ, | en |
| dc.relation.page | 98 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-09-11 | |
| 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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