Ferroptosis Is a Potential Therapeutic Target for Pulmonary Infectious Diseases

Figure 4

Ferroptosis and pulmonary infection caused by Mycobacterium tuberculosis. In the process of ferroptosis in host macrophages induced by acute lung necrosis induced by MTB, GPX4 levels are decreased and LPO, mitochondrial peroxide, free iron, and ROS are increased. The decreased level of GPX4 reduces its ability to decompose LPO, leading to the accumulation of LPO. ROS can also produce LPO through lipid peroxidation. At the same time, the increase of free iron leads to the increase of oxygen radicals produced by Fenton reaction. Both LPO and oxygen free radicals can damage cells. Iron supplementation promotes the Fenton reaction to produce oxygen free radicals and promotes the process of acute lung necrosis inducing host macrophage death, while the iron-chelating agent PIH inhibits this process by preventing Fenton reaction. Similarly, the ferroptosis inhibitor ferrostatin-1 inhibits this process by inhibiting lipid peroxidation. And HMOX1 can regulate the production of ROS and the increase of iron, thus changing the outcome of macrophage death after MTB infection. MTB: Mycobacterium tuberculosis; LPO: lipid peroxides; PIH: pyridoxal isonicotinoyl hydrazone; ROS: reactive oxygen species; GPX4: glutathione peroxidase 4; HMOX1: heme oxygenase-1.