Galectin-8 is a cytosolic lectin that functions as a danger receptor to defend cells against bacterial invasion by targeting damaged vesicles for autophagy. It monitors endo-lysosomal integrity and detects bacterial invasion by binding host glycans exposed on damaged Salmonella-containing vacuoles (SCVs). Galectin-8 recruits NDP52, an autophagy adaptor, to SCVs, activating anti-bacterial autophagy. This process is transient and followed by ubiquitin-dependent NDP52 recruitment. Galectin-8 also detects sterile damage to endosomes or lysosomes, as well as invasion by Listeria or Shigella, suggesting it serves as a versatile receptor for vesicle-damaging pathogens. The study shows that galectin-8 monitors the specific absence of complex carbohydrates in the cytosol to detect endo-lysosomal damage and initiate autophagy. Galectin-8 binds to glycans on damaged SCVs, which are exposed when the vesicles rupture, allowing galectin-8 to recognize host glycans and initiate autophagy. The recruitment of NDP52 to SCVs is mediated by two signals: a carbohydrate-dependent galectin-8 pathway and a ubiquitin-dependent pathway. The early response to invading bacteria requires the galectin-8-dependent pathway, while the zinc finger-dependent pathway dominates at later time points. Galectin-8 is positioned strategically at the cellular entry point for various pathogens and is expected to have shaped pathogen evolution. The study highlights the role of galectin-8 in autophagy-mediated defense against bacterial infection by monitoring endo-lysosomal integrity and recruiting NDP52 to target bacteria for autophagy. The findings contribute to understanding how cells defend against intracellular bacteria by activating autophagy at different stages of infection.Galectin-8 is a cytosolic lectin that functions as a danger receptor to defend cells against bacterial invasion by targeting damaged vesicles for autophagy. It monitors endo-lysosomal integrity and detects bacterial invasion by binding host glycans exposed on damaged Salmonella-containing vacuoles (SCVs). Galectin-8 recruits NDP52, an autophagy adaptor, to SCVs, activating anti-bacterial autophagy. This process is transient and followed by ubiquitin-dependent NDP52 recruitment. Galectin-8 also detects sterile damage to endosomes or lysosomes, as well as invasion by Listeria or Shigella, suggesting it serves as a versatile receptor for vesicle-damaging pathogens. The study shows that galectin-8 monitors the specific absence of complex carbohydrates in the cytosol to detect endo-lysosomal damage and initiate autophagy. Galectin-8 binds to glycans on damaged SCVs, which are exposed when the vesicles rupture, allowing galectin-8 to recognize host glycans and initiate autophagy. The recruitment of NDP52 to SCVs is mediated by two signals: a carbohydrate-dependent galectin-8 pathway and a ubiquitin-dependent pathway. The early response to invading bacteria requires the galectin-8-dependent pathway, while the zinc finger-dependent pathway dominates at later time points. Galectin-8 is positioned strategically at the cellular entry point for various pathogens and is expected to have shaped pathogen evolution. The study highlights the role of galectin-8 in autophagy-mediated defense against bacterial infection by monitoring endo-lysosomal integrity and recruiting NDP52 to target bacteria for autophagy. The findings contribute to understanding how cells defend against intracellular bacteria by activating autophagy at different stages of infection.