结核菌对造血干细胞进行重新编程,以限制骨髓形成和削弱训练后的免疫力
Nargis Khan1, Jeffrey Downey1, Joaquin Sanz2
1Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, Department of Pathology, McGill University, Montreal, QC, Canada; McGill International TB Centre, McGill University Health Centre, Montreal, QC, Canada.
结核菌 (Mtb) 感染通过干扰素-I (IFN-I) 反应对造血干细胞 (HSC) 进行重新编程,从而损害训练的免疫力. 这种免疫规避策略会破坏骨髓中的铁代谢和骨髓细胞发育.
科学领域:
- 免疫学
- 血液形成
- 传染性疾病
背景情况:
- 了解造血干细胞 (HSC) 调控对于治疗结核病等慢性感染至关重要.
- 之前的研究表明,Bacille Calmette- Guérin (BCG) 和β- 葡萄糖通过II型干扰素 (IFN- II) 或IN-1 (IL1) 在HSC中诱导受训免疫.
研究的目的:
- 为了研究Mycobacterium tuberculosis (Mtb) 如何重新编程HSC.
- 阐明Mtb干扰训练免疫力的机制.
主要方法:
- 对MTB感染反应的HSC重编程的分析.
- 对干扰素-I (IFN-I) 信号通路的研究.
- 在骨髓原体中评估铁代谢和线粒体功能.
- 在感染Mtb的小鼠中评估训练免疫的发展.
主要成果:
- 与BCG或β- 葡萄糖不同,mtb通过IFN- I反应重新编程HSC.
- IFN-I信号抑制骨髓形成并削弱对Mtb的保护性训练免疫力.
- Mtb诱导的IFN-I信号失调铁代谢,线粒体潜能,并导致骨髓原生细胞死亡.
- 在HSC中IFN-I/铁轴激活阻碍了对Mtb的训练免疫力.
结论:
- Mtb通过IFN-I信号来操纵骨髓中的免疫规避策略.
- 这种机制破坏了先天的免疫能力,并导致了慢性感染的持续.
更多相关视频
10:43Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
10:10A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection
Published on: October 5, 2015
相关概念视频
Pulmonary Tuberculosis I
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
Regulation of Hematopoietic Stem Cells
Pulmonary Tuberculosis V
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
Multipotency of Hematopoietic Stem Cells
Pulmonary Tuberculosis II
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
Cell-mediated Immune Responses
