Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems

Significance To combat infections with bacterial pathogens that reside and replicate inside specialized intracellular vacuoles, the innate immune system must be able to distinguish these pathogen-containing vacuoles (PVs) from endogenous vesicles. Here, we demonstrate that the host can detect the presence of bacterial secretion systems as hallmarks of PVs. The insertion of bacterial protein secretion pores destabilizes vesicular membranes, allowing host carbohydrate-binding proteins to access the sugar-decorated luminal side of vacuolar membranes. We show that a specific carbohydrate-binding protein recruits members of a family of antimicrobial GTPases to PVs. Our findings reveal how host cells deliver antimicrobial defenses specifically to intracellular vesicles occupied by pathogens.