Differential Host Gene Expression in Response to Infection by Different Mycobacterium tuberculosis Strains—A Pilot Study

Tuberculosis (TB) represents a global public health threat and is a leading cause of morbidity and mortality worldwide. Effective control of TB is complicated with the emergence of multidrug resistance. Yet, there is a fundamental gap in understanding the complex and dynamic interactions between different <i>Mycobacterium tuberculosis</i> strains and the host. In this pilot study, we investigated the host immune response to different <i>M. tuberculosis</i> strains, including drug-sensitive avirulent or virulent, and rifampin-resistant or isoniazid-resistant virulent strains in human THP-1 cells. We identified major differences in the gene expression profiles in response to infection with these strains. The expression of IDO1 and IL-1β in the infected cells was stronger in all virulent <i>M. tuberculosis</i> strains. The most striking result was the overexpression of many interferon-stimulated genes (ISGs) in cells infected with the isoniazid-resistant strain, compared to the rifampin-resistant and the drug-sensitive strains. Our data indicate that infection with the isoniazid-resistant <i>M. tuberculosis</i> strain preferentially resulted in cGAS-STING/STAT1 activation, which induced a characteristic host immune response. These findings reveal complex gene signatures and a dynamic variation in the immune response to infection by different <i>M. tuberculosis</i> strains.