Pharmacologic Inhibition of Macrophage Triglyceride Biosynthesis Pathways Does Not Improve Mycobacterium tuberculosis Control in Infected Mice.

ABSTRACT: Tuberculosis necrotic granulomas contain triglyceride-rich macrophages (foam cells) with reduced antimicrobial functions. We assessed the ability of 2 compounds to reduce the triglyceride content and Mycobacterium tuberculosis (Mtb) burden in infected human monocyte-derived macrophages and in the lungs of Mtb-infected C3HeB/FeJ mice: A-922500 (DGATi), an inhibitor of diacylglycerol O-acyltransferase 1, and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected macrophages. Each inhibitor reduced the cellular triglyceride content in bronchoalveolar lavage samples of Mtb-infected mice. After 6 weeks of treatment, p70S6Ki alone reduced the lung bacterial burden in Mtb-infected mice. However, DGATi alon

SUBMITTER: Ruelas Castillo J 

PROVIDER: S-EPMC12128068 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature