PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in hepatocytes.

Mycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia with debilitating loss of muscle mass. While anti-tuberculosis (TB) drug therapy is directed towards eliminating bacilli, the treatment regimen ignores the systemic pathogenic derailments that probably dictate TB-associated mortality and morbidity. Presently, it is not understood whether the spread of infection to other metabolic organs brings about these impairments. Here, we show that Mtb, during the chronic phase utilizes hepatocytes as a replicative niche and shields itself against the common anti-TB drugs by inducing drug-metabolizing enzymes. Mtb creates a replication-conducive milieu of lipid droplets in hepatocytes by upregulating transcription factor PPARγ. In the classical murine-TB aerosol infection model hepatocyte infection can be consistently observed post-week 4 along with enhanced expression of PPARγ and drug-metabolizing enzymes. Histopathological analysis and fluorescence in situ hybridization with Mtb-specific primers of human autopsy liver specimens, indeed show the presence of Mtb in hepatocytes along with granuloma-like structures. Hepatotropism of Mtb during the chronic infectious cycle results in immuno-metabolic dysregulation that could magnify local and systemic pathogenicity, altering clinical presentations ### Competing Interest Statement The authors have declared no competing interest.