树突细胞激活热和效应器触发的亡,以限制Legionella感染
Víctor R Vázquez Marrero1, Jessica Doerner1, Kimberly A Wodzanowski1,2
1Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
巨细胞和树突细胞 (DCs) 对细菌病原体产生不同的反应. DCs使用热和细胞灭来限制军团菌,Mcl-1和cFLIP保护宿主蛋白质合成.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 天生的免疫系统使用模式识别受体 (PRR) 和护卫蛋白来检测病原体和监测细胞过程.
- 了解不同免疫细胞如何利用这些传感器来应对感染至关重要,但人们对此了解甚少.
- 对细菌毒性因子的独特免疫细胞反应仍然是积极研究的领域.
研究的目的:
- 研究巨细胞和树突细胞 (DCs) 对细菌毒性活动的差异反应,特别是Legionella pneumophila.
- 阐明DCs在单细胞水平上检测和限制细胞内细菌病原体的机制.
- 确定特定宿主蛋白质 (如Mcl-1和cFLIP) 在感染期间保护细胞过程中的作用.
主要方法:
- 对巨细胞和树突细胞对*Legionella pneumophila*感染的反应进行比较分析.
- 单细胞分析以表征直流反应中的异质性.
- 调查caspase-11炎症酶激活,热和效应器触发的亡.
- 评估IV型分泌系统 (T4SS) 效应因子在宿主蛋白质合成抑制和Mcl-1和cFLIP枯竭中的作用.
主要成果:
- 巨细胞通过其IV型分泌系统 (T4SS) 支持强大的*Legionella pneumophila*复制.
- 树突细胞 (DCs) 呈现出不同的反应,T4SS活动触发了快速细胞死亡,限制了细菌的复制.
- 单细胞分析揭示了DCs的异质性:通过caspase-11和NLRP3炎症体的早期热亡,随后由T4SS效应体诱导的晚期热亡抑制蛋白质合成并耗尽Mcl-1和cFLIP.
结论:
- 在DC中,热和效应器触发的亡共同提供了强大的限制Legionella复制.
- Mcl-1和cFLIP的功能是守护蛋白,保护DCs中的宿主翻译.
- 巨细胞和DCs使用不同的先天免疫传感器和护卫蛋白,导致对细菌感染的反应不同.
更多相关视频
09:04Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
08:34Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
相关概念视频
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Cell-mediated Immune Responses
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
The Extrinsic Apoptotic Pathway
Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
