Unraveling ferroptosis in infectious diseases: From basics, mechanistic pathways, and its dual role in the infections to potential therapeutic implications

Abstract

Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid peroxides, distinguishing it from apoptosis, necrosis, and other cell death modalities. Initially examined to cancer and neurodegeneration, the recent data underscore its pivotal role in infectious illnesses. Across bacterial, viral, fungal, and parasitic diseases, this review offers a thorough investigation of how ferroptosis contributes to microbial infections. We investigate how different bacteria either promote pathogenicity, immunological evasion, or survival by using or modifying host ferroptotic processes. Moreover, we examine the host's ferroptotic response as a potential defense mechanism, its dual role in inflammation and tissue damage, and the interplay with immune signaling pathways. Understanding the mechanistic underpinnings of ferroptosis in infection may uncover novel therapeutic targets and strategies for infectious disease management. By integrating cross-kingdom perspectives, this paper is the first comprehensive review, which aims to highlight ferroptosis as a convergent point in host-pathogen interactions with significant biomedical implications.

Keywords: Bacterial infection; Ferroptosis; Fungal infection; Parasitic infection; Viral infection.