Alterations in the Immune Response in Individuals with Latent Tuberculosis Infection

Area of Science:

• Immunology
• Infectious Diseases
• Biomarker Discovery

Background:

• Latent tuberculosis infection (LTBI) is a persistent, asymptomatic stage of Mycobacterium tuberculosis (Mtb) infection.
• Subtle immunometabolic changes characterize LTBI, reflecting the host-pathogen balance.
• Understanding LTBI is critical for preventing progression to active tuberculosis (ATB).

Purpose of the Study:

• To review recent advances in identifying biomarkers for the preclinical phase of LTBI.
• To explore strategies for stratifying individuals at risk of LTBI reactivation.
• To discuss challenges and future directions in LTBI diagnostics and prevention.

Main Methods:

• Review of immunological, transcriptomic, metabolic, and imaging-based approaches.
• Analysis of quantitative assays (IGRA, TAM, MGIA) and transcriptional signatures.
• Consideration of experimental primate models and challenges in multidrug-resistant LTBI (MDR-LTBI).

Main Results:

• Multiple approaches, including IGRA, TAM tests, and interferon-related signatures, show predictive potential for LTBI reactivation.
• Functional assays and metabolic imaging (PET/CT) enhance predictive capabilities.
• Primate models aid in biomarker validation and strategy testing.

Conclusions:

• Integrating diverse data (immunological, transcriptomic, radiological) into risk-based screening can improve early detection and prevention of LTBI reactivation.
• Developing cost-effective, standardized diagnostic tools for LTBI requires international collaboration.
• Effective LTBI management, especially for MDR-LTBI, is crucial for TB control.