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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 張永祺(Yung-Chi Chang) | |
dc.contributor.author | Yu-Wen Tseng | en |
dc.contributor.author | 曾郁文 | zh_TW |
dc.date.accessioned | 2021-06-17T06:27:33Z | - |
dc.date.available | 2025-09-19 | |
dc.date.copyright | 2021-02-23 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-09-29 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72182 | - |
dc.description.abstract | 肺炎鏈球菌是一種格蘭氏陽性胞外菌,具有極高的致病率及致死率,尤其在孩 童及老人影響甚巨。因此,讓我們更迫切需要研究肺炎鏈球菌致病機轉及其與宿主 間的交互作用去找到預防及治療的方法。所有的肺炎鏈球菌臨床菌株皆有表現神 經氨酸酶,先前研究大多發現神經氨酸酶可以移除宿主細胞表面的唾液酸,並且 NanA 可幫助肺炎鏈球菌定殖在宿主組織上。我們先前的研究結果顯示肺炎鏈球菌 的神經氨酸酶移除宿主細胞表面的唾液酸後,可能會影響 TLR-2 與 Siglec-5 間的 交互作用,因而促使此細胞的 TNF-α表現量增加,並且會活化 MAPK, PI3k/Akt 和 NF-κB 等路徑。然而,神經氨酸酶如何調控宿主發炎的詳細機制目前仍不清楚,因 此於本篇論文中,我們將進一步探討神經氨酸酶影響發炎相關路徑的詳細機制,而 加劇宿主的發炎反應。實驗結果發現,具有神經氨酸酶的肺炎鏈球菌透過影響 TLR-2 下游分子 IKK complex 的活化,因而造成受感染的 THP-1 細胞中多種促發炎激 素表現量增加,包含 IL-1β , IL-8 和 TNF-α,此劇烈發炎的現象可能來自於神經氨 酸酶影響 Siglec-5 和 SHP-1 間的交互作用。另外,神經氨酸酶主要透過活化 NLRP3 inflammasome, Caspase-1,GSDMD 和部分影響 Caspase-8,而促進 IL-1β的產生,並 且造成受細胞的存活率降低。 | zh_TW |
dc.description.abstract | Streptococcus pneumoniae (SPN), a Gram-positive extracellular pathogen, causes high morbidity and mortality worldwide, especially in children and elderly. Therefore, understanding the molecular mechanism attributed to pneumococcal pathogenesis and bacteria-host interaction is crucial to develop novel therapeutics to combat pneumococcal infections. All SPN clinical isolates express neuraminidase A (NanA) which has been shown to target sialic acids expressing on the host cell surface and to promote SPN mucosal colonization. We recently demonstrated that NanA-mediated host cell desialylation is able to exacerbate TNF-α production through overactivation of the MAPK, PI3k/Akt and NF-kB pathways, which possibly resulted from dysregulation of the interaction between TLR-2 and Siglec-5. Given that the detailed mechanism regarding how NanA regulates host inflammation remains largely unknown, we aim to identify signaling pathways possibily contributed to this NanA-mediated immune exacerbation. In this study, we showed that WT SPN promotes the expression of multiple pro- inflammatory cytokines including IL-1β, IL-8, and TNF-α through activation of IκB kinase (IKK) in the infected THP-1 cells. This pneumococcal NanA-mediated cell activation may result from disrupting the interaction between Siglec-5 and SHP-1 phosphatase. Moreover, we also found that SPN NanA provokes the activation of NLRP3 inflammasome, Caspase-1, GSDMD, and part of Caspase-8, which together leading tomore IL-1β production and lower survival rate of infected cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T06:27:33Z (GMT). No. of bitstreams: 1 U0001-1909202020340300.pdf: 2739550 bytes, checksum: d72b9ee0e7b9c5afc18b526058065ae8 (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 口試委員會審定書··················································································i 致謝 ···································································································ii 中文摘要 ····························································································iii Abstract ······························································································iv 目錄 ··································································································vi 壹、研究背景與動機 ··············································································1 一、肺炎鏈球菌 (Streptococcus pneumoniae, SPN)·········································1 二、Sialic acid-binding immunoglobulin-like lectin (Siglec)································5 三、研究動機 ·······················································································8 貳、實驗材料與研究方法 ········································································9 一、實驗材料 ·······················································································9 二、研究方法 ····················································································· 11 參、研究結果 ····················································································· 19 一、肺炎鏈球菌 NanA 促進被肺炎鏈球菌感染之單核球細胞產生較多促發炎激素 ······································································································· 19 二、肺炎鏈球菌 NanA 改變單核球細胞之促發炎激素相關基因路徑 ··············· 19 三、肺炎鏈球菌 NanA 促進被肺炎鏈球菌感染之單核球細胞中 IKK 的磷酸化··· 21 四、肺炎鏈球菌 NanA 影響 Siglec-5 和 SHP-1 間的交互作用························· 21 五、肺炎鏈球菌 NanA 促進被肺炎鏈球菌感染之單核球細胞中 Caspase-1 的活化 並強化其 IL-1β 的產生 ········································································· 22 六、肺炎鏈球菌 NanA 可強化被肺炎鏈球菌感染之單核球細胞 NLRP3 inflammasome 活化 ·············································································· 24 七、 肺炎鏈球菌 NanA 造成被肺炎鏈球菌感染之單核球細胞活化較多 GSDMD且使細胞存活率降低 ··············································································· 25 八、 Caspase-8 參與在肺炎鏈球菌 NanA 造成單核球細胞 IL-1β的產生,並可能促進被感染之單核球細胞凋亡··································································· 27 九、缺乏 NanA 於肺炎鏈球菌結合單核球細胞及其 pneumolysin 表現量並無影響 ······································································································· 29 肆、討論與未來研究方向 ······································································ 31 參考文獻 ··························································································· 35 結果表格 ··························································································· 41 附錄 ································································································· 55 | |
dc.language.iso | zh-TW | |
dc.title | 肺炎鏈球菌NanA對於宿主細胞發炎及死亡之影響 | zh_TW |
dc.title | To investigate the role of Pneumococcal NanA in regulating host inflammation and cell death | en |
dc.type | Thesis | |
dc.date.schoolyear | 109-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 徐立中(Li-Chung Hsu),邱浩傑(Hao-Chieh Chiu) | |
dc.subject.keyword | 肺炎鏈球菌,神經氨酸酶,Sigle-5,TLR-2,NLRP3 inflammasome, | zh_TW |
dc.subject.keyword | Streptococcus pneumoniae,neuraminidase A,TLR-2,Siglec-5,NLRP3 inflammasome, | en |
dc.relation.page | 55 | |
dc.identifier.doi | 10.6342/NTU202004220 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-09-30 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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