Galectin-3 facilitates helicobacter pylori-induced apoptosis independently of sensing lysosomal damage.

Helicobacter pylori is a prevalent gastric pathogen that modulates host cell signaling pathways and represents a major risk factor for chronic gastritis, peptic ulcers, and gastric cancer. Galectin-3 is a host factor that contributes to immune regulation and cell death responses. However, its precise role in epithelial cell fate during H. pylori infection remains unclear. In this study, we demonstrate in AGS epithelial cells that H. pylori infection induces the accumulation of cytosolic galectin-3 around lysosomes damaged by the infection, detectable as puncta formation, and this process requires the presence of O-glycan. Using galectin-3 knockout cells, we show that galectin-3 expression correlates with the extent of apoptosis triggered by infection, which proceeds independently of VacA (vacuolating cytotoxin A). Pharmacological inhibition of galectin-3 glycan binding prevents lysosomal puncta formation but does not diminish apoptosis, indicating that galectin-3 promotes cell death through glycan-independent protein-protein interactions. Moreover, galectin-3 puncta co-localize with LC3-positive autophagosomal structures, and functional assays reveal that the initiation of autophagy facilitates apoptosis. Collectively, these findings identify galectin-3 as a pro-apoptotic factor involved in the epithelial response to H. pylori infection.