Figure 3.

Pyroptosis and ferroptosis in H. pylori infection. In pyroptosis, H. pylori and its virulence factors (e.g. CagA, VacA, UreB) trigger the inflammatory cascade of NLRP3, which leads to the activation of caspase-1. Caspase-1 cleaves pro-IL-1β to generate its active form and also targets GSDMD, leading to recruitment of the N-terminal fragment of GSDMD to the plasma membrane. This leads to pore formation and the subsequent release of inflammatory factors. Upon ferroptosis, H. pylori and its OMVs upregulate Solute Carrier Family 3 Member 2 (SLC3A2) to attenuate ferroptosis, while repressing lysophosphatidylcholine acyltransferase 3 (LPCAT3) and downregulating transferrin receptor 1 (TfR1) to attenuate lipid peroxidation. H. pylori may also increase susceptibility to RAS-selective lethality 3 (RSL3)-induced ferroptosis by influencing associated genes.