Cell state transition analysis identifies interventions that improve control of Mycobacterium tuberculosis infection by susceptible macrophages

• DOI: 10.1126/sciadv.adh4119
• Publication Date: 2023-09-27T17:59:10Z
• Authors: Shivraj M. Yabaji; Oleksii S. Rukhlenko; Sujoy Chatterjee; Bidisha Bhattacharya; Emily Wood; Marina Kasaikina; Boris N. Kholodenko; Alexander A. Gime...; Igor Kramnik
• Keywords: Mice; 0303 health sciences; 03 medical and health sciences; Tumor Necrosis Factor-alpha; Macrophages; Animals; Tuberculosis; Biomedicine and Life Sciences; Mycobacterium tuberculosis; Disease Susceptibility

Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research medicine. Here, we identify transcriptional signature that distinguishes activated macrophages from the tuberculosis (TB) susceptible resistant mice. We then apply cSTAR (cell transition assessment regulation) approach data screening-by-RNA sequencing chemical perturbations shift of tumor necrosis factor (TNF)-activated TB-susceptible toward TB-resistant cells, i.e., prevents their aberrant activation without suppressing beneficial TNF responses. Last, demonstrate compounds identified with this enhance resistance mouse virulent Mycobacterium tuberculosis.