Ferroptosis is an iron-dependent form of regulated necrotic cell death driven by uncontrolled lipid peroxidation. During Mycobacterium tuberculosis (Mtb) infection, disturbances in iron homeostasis and antioxidant defenses can sensitize macrophages and epithelial cells to ferroptotic injury, which may contribute—together with apoptosis, necroptosis, pyroptosis and other death programs—to necrosis, cavitation and bacterial dissemination. This review summarizes current evidence linking ferroptosis to tuberculosis (TB), focusing on (i) host–pathogen mechanisms that shape ferroptosis, including host iron handling and redox/lipid remodeling as well as Mtb-secreted effectors (e.g., PtpA, Rv1324, PPiA, Rv2521 and Mb3523c) that rewire these networks; (ii) pathological associations with granuloma necrosis, immunopathology and bacterial dissemination; (iii) ferroptosis-related gene/miRNA signatures proposed as biomarkers, together with limitations in cohort size, confounding comorbidities and external validation; and (iv) translational opportunities and caveats for host-directed therapy, including ferroptosis inhibitors, iron modulation and targeted delivery systems. Finally, we outline key safety and pharmacologic gaps that must be addressed before clinical application.
Ye et al. (Mon,) studied this question.