Die another way: Ferroptosis drives tuberculosis pathology

Abstract

In this issue of JEM, Amaral et al. (https://doi.org/10.1084/jem.20181776) provide the first evidence that ferroptosis, a newly described form of regulated cell death, is detrimental for the host during a Mycobacterium tuberculosis infection. This finding has important implications for the development of host-directed therapies for tuberculosis.

Insights from Etienne Meunier and Olivier Neyrolles.

Ferroptosis drives tuberculosis pathology. Upon macrophage infection by M. tuberculosis, increased levels of labile iron promote ROS-dependent lipid peroxidation. Accumulation of lipid peroxides induces plasma membrane destabilization, leading to ferroptosis-mediated cell death. Ferroptosis drives tissue necrosis and allows M. tuberculosis to thrive and spread, probably due to iron availability and the lack of an efficient macrophage antimicrobial immune response.