Differential Host Gene Expression in Response to Infection by Different Mycobacterium tuberculosis Strains-A Pilot...

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• Tuberculosis (TB) is a major global health issue, complicated by multidrug resistance.
• Understanding host-pathogen interactions with diverse Mycobacterium tuberculosis strains is crucial but limited.

Purpose of the Study:

• To investigate host immune responses to different M. tuberculosis strains.
• To compare gene expression profiles following infection with drug-sensitive and resistant strains.

Main Methods:

• Pilot study using human THP-1 cells.
• Infection with drug-sensitive (avirulent/virulent) and drug-resistant (rifampin/isoniazid) M. tuberculosis strains.
• Analysis of host gene expression profiles.

Main Results:

• Significant differences in gene expression were observed across M. tuberculosis strains.
• Virulent strains induced higher expression of IDO1 and IL-1β.
• The isoniazid-resistant strain uniquely overexpressed interferon-stimulated genes (ISGs).
• Isoniazid-resistant strain infection activated the cGAS-STING/STAT1 pathway.

Conclusions:

• Host immune responses vary dynamically with M. tuberculosis strain type.
• Isoniazid-resistant strains elicit a distinct immune signature involving ISGs and cGAS-STING/STAT1.
• Findings highlight complex gene signatures and immune variations in TB pathogenesis.