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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 伍安怡 | |
dc.contributor.author | Hsiu-Chao Lin | en |
dc.contributor.author | 林修兆 | zh_TW |
dc.date.accessioned | 2021-06-15T06:58:20Z | - |
dc.date.available | 2016-10-05 | |
dc.date.copyright | 2011-10-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-19 | |
dc.identifier.citation | Altenbach D, Robatzek S. Pattern recognition receptors: from the cell surface to intracellular dynamics. Mol Plant Microbe Interact 2007;20:1031–9.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48475 | - |
dc.description.abstract | 組織胞漿菌是一種雙型態的真菌,自然狀況下以菌絲的型態生長於酸性土壤中,一旦吸入動物體內,形成在寄主細胞內的胞內菌,會寄生在巨噬細胞吞噬小體內進行繁衍;另一方面,組織胞漿菌感染樹突狀細胞後能夠最為抗原呈現細胞刺激免疫T細胞。我的實驗中,巨噬細胞或樹突細胞吞噬組織胞漿菌之後,刺激caspase-1的活化並且產生IL-1β;另一方面,在組織胞漿菌感染的動物實驗中也從脾臟和血清中測得IL-1β的產生,然而是如何被組織胞漿菌活化產生IL-1β的機制目前仍不清楚
目前研究比較透徹的三個家族成員,如NLRC4(也被稱為IPAF)、NLRP1和NLRP3(亦可稱cryopyrin或是NALP3),這三個NLR是細胞內蛋白,並且可以形成一個稱為炎性體(inflammasomes)的複合體,這一個複合體有顯著的半胱胺酸蛋白脢(caspase-1)活化作用。在我的研究中想探討組織胞漿菌和巨噬細胞或樹突狀細胞之間的相互作用產生炎性體的機制。將骨髓幹細胞分化的巨噬細胞和樹突狀細胞感染後,研究炎性感染組織胞漿。結果顯示,組織胞漿菌感染的巨噬細胞和樹突狀細胞的同時誘導半胱胺酸蛋白脢激活和IL-1β的產生。另一方面,實驗利用knockdown NLRP3的THP-1細胞感染組織胞漿菌,發現炎性體的活化必須藉由NLRP3才能達成,從而影響IL-1β的分泌。 為了進一步探討在小鼠對抗組織胞漿菌中所扮演的角色,我利用了巨噬細胞及樹突細胞的表面受器(receptor),可能會參與辨認以及吞噬組織胞漿菌的作用前提下,用抗體抑制不同表面受器進而探討對於炎性體以及IL-1β產生的影響,結果發現IL-1β分泌和半胱胺酸蛋白脢的活化,在巨噬細胞需要藉由CR3受體,而在樹突狀細胞中需要Dectin-2、甘露糖受體或是TLR2辨認後活化。 從已發表的文獻中了解到參與活化炎性體相對應的分子蛋白,這些蛋白對於下游訊息傳遞過程扮演非常重要的角色,在此研究中我探討組織胞漿菌感染巨噬細胞和樹突細胞後,是否會活化MAPK的訊息傳遞分子。結果顯示,組織胞漿菌會引起Syk、ERK、JNK和p38的磷酸化,而在抑制Syk、ERK、JNK後會抑制半胱胺酸炎性體的激活和IL-1β分泌,但抑制p38並不會有此影響。這些結果表明,在巨噬細胞中,組織胞漿菌感染引發NLRP3炎性激活需要藉由CR3受體,而在樹突狀細胞中需要多種受體。並且在巨噬細胞和樹突狀細胞都需要藉由Syk、ERK和JNK的磷酸化來活化炎性體。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:58:20Z (GMT). No. of bitstreams: 1 ntu-100-R98449002-1.pdf: 2293301 bytes, checksum: e07679695c9f7ee102225da7251c51e7 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | Content
English Abstract........................................................................................................... i Chinese Abstract.......................................................................................................... iii Abbreviations................................................................................................................ v Content.......................................................................................................................... vi List of Figures......................................................................................................... xi I. Introduction.............................................................................................................. 1 1. Histoplama capsulatum........................................................................................ 2 1.1 Histoplasma capsulatum fungus ……......................................................... 2 1.2 Histoplasma capsulatum infection............................................................... 2 1.3 Intracellular localization of Histoplasma capsulatum................................. 4 1.4 Host defense against Histoplasma capsulatum............................................ 5 1.5 The mechanism of host-cell binding and specific receptors interaction........... 7 2. Innate immunity................................................................................................... 9 2.1 Pattern recognition....................................................................................... 9 2.2 The NLR Family.......................................................................................... 10 2.3 Inflammasomes............................................................................................ 11 2.4 NALP1 and NLRC4.................................................................................... 12 2.5 NALP3......................................................................................................... 13 3. Pathogens stimulate inflammasome infection...................................................... 15 3.1 Infection by intracellular bacterial pathogens.............................................. 16 3.2 Mycobacterium tuberculosis........................................................................ 17 3.3 Listeria monocytogenes................................................................................ 18 3.4 Staphylococcus aureus................................................................................. 19 3.5 Fungi............................................................................................................ 20 II. Aim of The Study………......................................................................................... 23 Specific Aims..................................................................................................... 24 III. Materials and Methods......................................................................................... 27 Part I. Materials........................................................................................................ 28 1. Mice............................................................................................................... 28 2. Antibody......................................................................................................... 28 3. Solution.......................................................................................................... 30 4. Chemical and reagents................................................................................... 32 5. Equipments..................................................................................................... 35 Part II. Methods........................................................................................................ 36 IV. Results..................................................................................................................... 44 1. IL-1β is detected in the spleen and serum of Histoplasma infected mice.......... 45 2. Mouse macrophages and dendritic cells secret IL-1β after Histoplasma infection............................................................................................................. 45 3. Histoplasma also induces caspase-1 activation and pro-IL-1β synthesis in human macrophages........................................................................................... 47 4. Histoplasma infection induces NLRP3-dependent inflammasome in THP-1 cell...................................................................................................................... 48 5. Histoplasma infection or LPS stimulation does not induce cell death.............. 48 6. Receptor expression on BMDM and BMDC.........................................……… 49 7. Blocking BMDMs/BMDCs receptors effects IL-1β secretion........................... 49 8. Histoplasma infection induces Syk and MAPK signaling in BMDM and BMDC.......................................…….................................................………… 50 9. Histoplasma infection activates inflammasome through ERK and JNK phosphorylation.......................................…….......................................……… 51 V. Discussion................................................................................................................. 53 1. IL-1β production protects mice from Histoplasma infection............................. 54 2. NLRP3 infalmmasome responses to Histoplasma infection.............................. 56 3. Different receptors are involved in BMDM and BMDC IL-1β, TNF and IL-6 response to Histoplasma.................................................................................... 59 4. Dectin-2 as a receptor to interact with Histoplasma.......................................... 62 5. IL-1β production is Syk phosphorylation-dependent......................................... 63 6. Distinct MAPK signaling molecules are involved in the production of different cytokines after Histoplasma infection................................................. 64 7. The relationship between cell surface receptors on BMDM and BMDC for Histoplasma and MAPK signaling pathway leading to inflammasome activation............................................................................................................ 66 8. Conclusions........................................................................................................ 67 VI. References............................................................................................................... 69 VII. Figures................................................................................................................... 82 | |
dc.language.iso | en | |
dc.title | 探討組織胞漿菌引發巨噬細胞及樹突細胞炎性體的活化 | zh_TW |
dc.title | Histoplasma capsulatum infection induces inflammasome activation in macrophages and dendritic cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 李建國,徐立中 | |
dc.subject.keyword | 組織胞漿菌,巨噬細胞,樹突細胞,炎性體,半胱胺酸蛋白脢, | zh_TW |
dc.subject.keyword | Histoplasma capsulatum,macrophages,dendritic cells,inflammasome,caspase-1, | en |
dc.relation.page | 107 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-19 | |
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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