Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis.

Abstract

Mycobacterium tuberculosis ( Mtb ) primarily infects macrophages in the lungs. In infected macrophages, Mtb uses host lipids as key carbon sources to maintain infection and survive. In this work, we used a CRISPR-Cas9 gene knockout system in murine macrophages to examine the role of host fatty acid metabolism on the intracellular growth of Mtb . Our work shows that macrophages which cannot either import, store or catabolize fatty acids restrict Mtb growth by both common and divergent anti-microbial mechanisms, including increased glycolysis, increased production of reactive oxygen species, production of pro-inflammatory cytokines, enhanced autophagy and nutrient limitation. Our findings demonstrate that manipulating lipid metabolism in macrophages controls Mtb through multiple other mechanisms, beyond limiting the bacteria's access to nutrients.