The fat is in the lysosome: how Mycobacterium tuberculosis tricks macrophages into storing lipids
Yoann Rombouts, Olivier Neyrolles
Yoann Rombouts, Olivier Neyrolles
Published March 15, 2023
Citation Information: J Clin Invest. 2023;133(6):e168366. https://doi.org/10.1172/JCI168366.
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Commentary

The fat is in the lysosome: how Mycobacterium tuberculosis tricks macrophages into storing lipids

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects primarily macrophages, causing them to differentiate into lipid-laden foamy macrophages that are a primary source of tissue destruction in patients with TB. In this issue of the JCI, Bedard et al. demonstrate that 1-tuberculosinyladenosine, a virulence factor produced by M. tuberculosis, caused lysosomal dysfunction associated with lipid storage in the phagolysosome of macrophages in a manner that mimicked lysosomal storage diseases. This work sheds light on how M. tuberculosis manipulates host lipid metabolism for its survival and opens avenues toward host-directed therapy against TB.

Authors

Yoann Rombouts, Olivier Neyrolles

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Figure 1

1-TbAd produced by M. tuberculosis induces lysosomal lipid storage.

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1-TbAd produced by M. tuberculosis induces lysosomal lipid storage. (i) ...
(i) M. tuberculosis (Mtb) produces 1-TbAd, which raises the vacuolar pH and inhibits acidic hydrolases, including lipases, inside the phagolysosome. (ii) Consequently, lipids, including cholesteryl esters and triglycerides, accumulate in the vacuole, mimicking lysosomal storage diseases. (iii) Under conditions of restricted lipid access, M. tuberculosis can use these lipids as a carbon source to promote its intracellular growth.