AIRE缺陷影响巨噬细胞对白色念珠菌的应答作用
发布时间：2021-08-12 07:03
自身免疫调节因子（AIRE）作为转录因子主要表达在胸腺髓质上皮细胞中,负责提呈不同组织特异性抗原进而促进T细胞的阴性选择及其发育成熟。此外,AIRE也能够促进调节性T细胞的发育。AIRE基因突变可导致多器官的自身免疫病和皮肤粘膜念珠菌病,即APECED,该患者体内通常会产生针对不同腺体组织,如睾丸、卵巢和甲状腺等的自身抗体。AIRE基因也表达在胸腺外的不同部位,如次级淋巴器官、单核巨噬细胞中,诱导清除中枢耐受逃逸的自身反应性T细胞。也有研究显示AIRE也可用于治疗移植物抗宿主病。一些研究发现胸腺外表达的AIRE可能通过调控PRR表达和抗原提呈细胞的MHC分子,在局部组织免疫应答中发挥重要作用。AIRE缺陷患者更易感念珠菌病,而正常机体主要通过巨噬细胞和树突状细胞介导的固有免疫发挥抗念珠菌作用。因此为了探讨AIRE对巨噬细胞应答白色念珠菌中的作用,本研究主要通过白色念珠菌体外刺激AIRE敲除鼠腹腔巨噬细胞检测M1相关分子及PRR表达,以及建立白色念珠菌感染的AIRE敲除鼠模型进一步研究,结果发现:1.在体外,AIRE敲除鼠腹腔巨噬细胞在对白色念珠菌应答时,M1型巨噬细胞相关分子IL-6及...
【文章来源】：吉林大学吉林省 211工程院校 985工程院校 教育部直属院校
【文章页数】：84 页
【学位级别】：硕士
【文章目录】：
提要
Preface
中文摘要
abstract
Abbreviations
1 Literature review
1.1 AIRE as an important regulator for T cell development
1.1.1 Mechanism of tolerance at thymus
1.1.2 Molecular features of AIRE functioning
1.2 AIRE ahead of auto antigens
1.3 Anti-tumor immunity of AIRE
1.4 TSA independent functions of AIRE
1.5 Activity of AIRE in GVHD
1.6 Extra thymic expression of AIRE and its role in peripheral tolerance
1.6.1 AIREs tissue and cellular distributions
1.6.2 AIRE's function in peripheral immune tolerance
1.7 Immune Response to Candida albicans
1.7.1 Antimicrobial proteins against Candida albicans
1.8 Response of Macrophage to Candida albicans components
1.8.1 Recognition ofβ-1,6-glucans of Candida albicans by Dectin-1 of macrophage
1.8.2 Macrophages response to cell wall chitin
1.8.3 Mannoprotiens interaction with macrophage
1.9 Proinflammatory macrophages M1 and anti-inflammatory M2 and their response to Candida albicans
1.10 Secretion of cytokines in the response of Candida albicans
1.11 Candida albicans infections as a common consequences of APECED patients
2 Study design
3 Material and method
3.1 Materials
3.1.1 Mice
3.1.2 Candida albicans strain
3.1.3 Main reagents
3.1.4 Main equipment
3.1.5 Reagents preparation
3.2 Methods
3.2.1 Isolation and polarization of mice peritoneal macrophage
3.2.2 Flow cytometry
3.2.3 Establishment of systemic candidiasis model
3.2.4 Macrophage and candida albicans co-culturing
3.2.5 RNA isolation and RT-qPCR analysis
3.2.6 Statistical Analysis
4 Results
4.1 Effects of AIRE deficiency on macrophage response to Candida albicans in vitro.
4.1.1 The culture of Candida albicans
4.1.2 The macrophage isolation and identification from mice peritoneal cavity
4.1.3 The stimulation of Candida albicans to macrophage
4.1.4 Effects of AIRE on expression of M1 associated molecules in response to Candida albicans
4.1.5 Effects of AIRE on PRR expression of macrophages in response to Candida albicans
4.2 Effects of AIRE deficiency on the macrophage response to Candida albicans in vivo
4.2.1 Observation of the general status of Candida albicans infected mice
4.2.2 The effect of AIRE deficiency on the histological pathology in mice with Candida albicans infection
4.2.3 The isolation and identification of peritoneal cavity macrophage from mice with Candida albicans infection
4.2.4 The effect of AIRE deficiency on M1 related molecules expression in macrophage from Candida albicans infected mice
4.2.5 The effect of AIRE deficiency on the survival of mice with Candida albicans infection
5 Discussion
6 Conclusion
References
Short introduction of the writer and attainment throughout research at school
Acknowledgement
本文编号：3337837
【文章来源】：吉林大学吉林省 211工程院校 985工程院校 教育部直属院校
【文章页数】：84 页
【学位级别】：硕士
【文章目录】：
提要
Preface
中文摘要
abstract
Abbreviations
1 Literature review
1.1 AIRE as an important regulator for T cell development
1.1.1 Mechanism of tolerance at thymus
1.1.2 Molecular features of AIRE functioning
1.2 AIRE ahead of auto antigens
1.3 Anti-tumor immunity of AIRE
1.4 TSA independent functions of AIRE
1.5 Activity of AIRE in GVHD
1.6 Extra thymic expression of AIRE and its role in peripheral tolerance
1.6.1 AIREs tissue and cellular distributions
1.6.2 AIRE's function in peripheral immune tolerance
1.7 Immune Response to Candida albicans
1.7.1 Antimicrobial proteins against Candida albicans
1.8 Response of Macrophage to Candida albicans components
1.8.1 Recognition ofβ-1,6-glucans of Candida albicans by Dectin-1 of macrophage
1.8.2 Macrophages response to cell wall chitin
1.8.3 Mannoprotiens interaction with macrophage
1.9 Proinflammatory macrophages M1 and anti-inflammatory M2 and their response to Candida albicans
1.10 Secretion of cytokines in the response of Candida albicans
1.11 Candida albicans infections as a common consequences of APECED patients
2 Study design
3 Material and method
3.1 Materials
3.1.1 Mice
3.1.2 Candida albicans strain
3.1.3 Main reagents
3.1.4 Main equipment
3.1.5 Reagents preparation
3.2 Methods
3.2.1 Isolation and polarization of mice peritoneal macrophage
3.2.2 Flow cytometry
3.2.3 Establishment of systemic candidiasis model
3.2.4 Macrophage and candida albicans co-culturing
3.2.5 RNA isolation and RT-qPCR analysis
3.2.6 Statistical Analysis
4 Results
4.1 Effects of AIRE deficiency on macrophage response to Candida albicans in vitro.
4.1.1 The culture of Candida albicans
4.1.2 The macrophage isolation and identification from mice peritoneal cavity
4.1.3 The stimulation of Candida albicans to macrophage
4.1.4 Effects of AIRE on expression of M1 associated molecules in response to Candida albicans
4.1.5 Effects of AIRE on PRR expression of macrophages in response to Candida albicans
4.2 Effects of AIRE deficiency on the macrophage response to Candida albicans in vivo
4.2.1 Observation of the general status of Candida albicans infected mice
4.2.2 The effect of AIRE deficiency on the histological pathology in mice with Candida albicans infection
4.2.3 The isolation and identification of peritoneal cavity macrophage from mice with Candida albicans infection
4.2.4 The effect of AIRE deficiency on M1 related molecules expression in macrophage from Candida albicans infected mice
4.2.5 The effect of AIRE deficiency on the survival of mice with Candida albicans infection
5 Discussion
6 Conclusion
References
Short introduction of the writer and attainment throughout research at school
Acknowledgement
本文编号：3337837
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