Expression of nuclear factor, erythroid 2-like 2-mediated genes differentiates tuberculosis

Area of Science:

• Molecular Biology
• Immunology
• Infectious Diseases

Background:

• Nuclear factor, erythroid 2-like 2 (Nrf2) is a key regulator of antioxidant responses during infection.
• Tuberculosis (TB) remains a leading infectious disease killer globally, necessitating improved diagnostic and therapeutic strategies.
• Understanding Nrf2's role in TB pathogenesis is critical for developing novel interventions.

Purpose of the Study:

• To identify genes regulated by Nrf2 in the context of TB.
• To develop a gene signature for TB diagnosis and treatment monitoring.
• To elucidate the role of Nrf2-mediated signaling in TB.

Main Methods:

• Meta-analysis of gene expression datasets from control, Nrf2-deficient, and TB patient samples.
• Comparison of gene expression profiles between TB patients and healthy, pneumonia, and lung cancer cohorts.
• Identification and validation of a 17-gene signature associated with Nrf2 activity and TB.

Main Results:

• A significant overlap was found between Nrf2-mediated genes and genes deregulated in TB.
• An Nrf2-mediated 17-gene signature was identified, reflecting key TB-related biological processes.
• The 17-gene signature effectively distinguished TB patients from various control groups and indicated therapeutic response.

Conclusions:

• Nrf2 plays a central role in TB pathogenesis.
• The identified 17-gene signature serves as a novel diagnostic biomarker for TB.
• This Nrf2-mediated gene signature offers a promising tool for differentiating TB and monitoring treatment efficacy.