Galectin-8, a cytosolic lectin, acts as a danger receptor to restrict Salmonella proliferation by monitoring endo-lysosomal integrity and detecting bacterial invasion through binding host glycans exposed on damaged Salmonella-containing vacuoles. Galectin-8 recruits NDP52, an autophagy receptor, to these vesicles, activating anti-bacterial autophagy. The recruitment of NDP52 by galectin-8 is transient and followed by ubiquitin-dependent recruitment. Galectin-8 also detects sterile damage to endosomes or lysosomes and invasion by other pathogens like Listeria and Shigella, suggesting its versatility as a receptor for vesicle-damaging pathogens. The study highlights how cells deploy galectin-8 to combat infection by monitoring endo-lysosomal integrity based on the specific lack of complex carbohydrates in the cytosol.Galectin-8, a cytosolic lectin, acts as a danger receptor to restrict Salmonella proliferation by monitoring endo-lysosomal integrity and detecting bacterial invasion through binding host glycans exposed on damaged Salmonella-containing vacuoles. Galectin-8 recruits NDP52, an autophagy receptor, to these vesicles, activating anti-bacterial autophagy. The recruitment of NDP52 by galectin-8 is transient and followed by ubiquitin-dependent recruitment. Galectin-8 also detects sterile damage to endosomes or lysosomes and invasion by other pathogens like Listeria and Shigella, suggesting its versatility as a receptor for vesicle-damaging pathogens. The study highlights how cells deploy galectin-8 to combat infection by monitoring endo-lysosomal integrity based on the specific lack of complex carbohydrates in the cytosol.