在Candida glabrata中,SWI/SNF复杂介导的染色体重塑促进了免疫逃避
Kundan Kumar1, Aditi Pareek1,2, Rupinder Kaur1
1Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500039, India.
iScience
|April 18, 2024
概括
甘虫使用染色体重塑来逃避免疫细胞. CgSnf2控制抑制或刺激免疫反应的基因,影响真菌毒性和宿主炎症.
科学领域:
- 菌类学 菌类学是指菌类学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 免疫逃避对菌病原体的毒性至关重要,例如Candida glabrata (Cg).
- 通过Cg逃避宿主免疫系统的机制,特别是在巨细胞内,仍然在很大程度上是未知的.
- 了解CG的免疫逃避策略对于开发有效的抗真菌疗法至关重要.
研究的目的:
- 调查染色体重塑在Cg与巨细胞相互作用中的作用.
- 在巨细胞内部化过程中通过染色质重组调节的特定基因和通路的识别.
- 阐明Cg的表观遗传修饰与宿主免疫反应之间的联系.
主要方法:
- 产生了第一个全基因组核细胞图,用于巨细胞内化Cg.
- 通过CgSnf2 (SWI/SNF染色体重塑复合体-ATPase子单元) 中介的基因表达变化的分析.
- 在对Cg进行基因操纵后,对巨细胞中的IL-1β产生和Cg增殖的评估.
主要成果:
- 在CgSnf2中介的染色质重组中,有差异性地调节了曼诺西转移酶集群 (CgMT-C) 和EPA1基因.
- EPA1的上调和CgMT-C的下调增强了IL-1β的产生,并减少了巨细胞中的Cg增殖.
- 删除CgSnf2 (Cgsnf2Δ) 会导致Epa1表达的增加,IL-1β分泌的增加以及巨细胞清除的受损.
结论:
- 核细胞定位和染色体重塑与Cg中的免疫调节分子的表达直接相关.
- 通过表观遗传调节,CgSnf2在调节Cg与宿主免疫系统的相互作用方面发挥着至关重要的作用.
- NF-κB信号传递是巨细胞对坎迪达菌感染反应的关键途径,突出显示了它在真菌病原性中的重要性.
相关概念视频
02:54Nucleosome Remodeling
9.1K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.1K
01:32Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
01:57Protein Complexes with Interchangeable Parts
2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K