Inhibition of granuloma triglyceride synthesis imparts control of Mycobacterium tuberculosis through curtailed inflammatory responses

We report the impact of granuloma triglyceride lowering on progression of infection in the C3HeB/FeJ mouse model. Triglyceride lowering was acheived by intravenous administration of the DGAT1 (diacylglycerol O-acyltransferase 1) inhibitor T863. C3HeB/FeJ mice were infected at high dose (500 cfu) with Mycobacterium tuberculosis Erdman strain, and then treated either with T863 or vehicle control from d8 to d28. T863 treated mice exhibited a heterogenous response to treatment in terms of bacterial control. A "High cfu"group exhibited no difference in CFU compared to vehicle treated mice (control) while a "low cfu"group exhibited 97-25% reduction in CFU compared to control mice. RNA-seq was performed on lung tissue from these mice.