结核分枝杆菌
肺结核
肿瘤坏死因子α
毒力
过渡(遗传学)
巨噬细胞
细胞
微生物学
免疫学
生物
医学
计算生物学
基因
遗传学
体外
病理
作者
Shivraj M. Yabaji,Oleksii S. Rukhlenko,Sujoy Chatterjee,Bidisha Bhattacharya,Emily Wood,Marina V. Kasaikina,Boris N. Kholodenko,Alexander A. Gimelbrant,Igor Kramnik
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-09-29
卷期号:9 (39)
被引量:2
标识
DOI:10.1126/sciadv.adh4119
摘要
Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research and medicine. Here, we identify a transcriptional signature that distinguishes activated macrophages from the tuberculosis (TB) susceptible and resistant mice. We then apply the cSTAR (cell state transition assessment and regulation) approach to data from screening-by-RNA sequencing to identify chemical perturbations that shift the transcriptional state of tumor necrosis factor (TNF)-activated TB-susceptible macrophages toward that of TB-resistant cells, i.e., prevents their aberrant activation without suppressing beneficial TNF responses. Last, we demonstrate that the compounds identified with this approach enhance the resistance of the TB-susceptible mouse macrophages to virulent Mycobacterium tuberculosis.
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