This thesis uncovers an ancestral intracellular surveillance system based on glycan recognition. Using Dictyostelium discoideum infected with Mycobacterium marinum, we show that bacterial surface glycolipids are shed early during infection and disseminate to neighboring cells, triggering a transcriptional response before cytosolic escape. We identify discoidins, cytosolic lectins with dual DS and H-type domains, as key effectors that specifically recognize non-self glycans exposed upon vacuolar damage. Through genetic, biochemical, and imaging analyses, discoidins are shown to bind pathogen-derived glycolipids such as LOS and PGL and to coordinate the recruitment of ESCRT and autophagy pathways for membrane repair. The absence of discoidins in the host leads to delayed damage sensing, defective repair, and restricted bacterial cytosolic access. Altogether, these findings reveal discoidins as evolutionary precursors of cytosolic lectins that couple non-self glycan recognition with compartmentalized innate immune activation and control of intracellular infection.