Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease
| Autor: | Cecilia S. Lindestam Arlehamn, Bjoern Peters, Eneida A. Parizotto, Tom Fletcher, Matthew K. O'Shea, Akul Singhania, Timothy C. Rodwell, Helen McShane, Martin Dedicoat, Rachel Tanner, James Dunbar, Adam F. Cunningham, Julie G. Burel, Paige Dubelko, Antonino Catanzaro, Donald G. Catanzaro, Julius Muller |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Adult Male Tuberculosis Immunology Disease Medical and Health Sciences Microbiology State Medicine Article Transcriptome Immune system Rare Diseases Clinical Research Latent Tuberculosis medicine Genetics Humans Prophylaxis treatment Longitudinal Studies wf_215 Latent tuberculosis business.industry Transmission (medicine) Gene Expression Profiling Blood transcriptomics Mycobacterium tuberculosis Middle Aged medicine.disease bacterial infections and mycoses Infectious Diseases Good Health and Well Being England Tissue Array Analysis Case-Control Studies Cohort Chemoprophylaxis Female qu_450 wf_200 business Infection qy_450 |
| Zdroj: | Tuberculosis (Edinb) |
| ISSN: | 1472-9792 |
| Popis: | Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large. |
| Databáze: | OpenAIRE |
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