Deglycosylation at War: Host N-Glycoprotein Remodeling in Infection and Immunity

N-glycan remodeling, including the hydrolysis of both glycopeptide linkages and glycosidic linkages, serves as a critical regulatory mechanism in biological processes including molecular recognition and immune responses. Growing evidence reveals that the dynamic balance between host protein glycosylation and N-glycan remodeling significantly influences the outcomes of infectious diseases. During infection, host N-glycoproteins remodeling can be driven either by the host as a defense strategy or by pathogens as an offensive mechanism. This review systematically examines how both host- and pathogen-induced N-glycan remodelling events affect infection outcomes. We highlight the dual functionality: host-driven remodeling often enhances immune recognition and pathogen clearance, whereas pathogen-driven remodeling facilitates adhesion, immune evasion, and nutrient acquisition. By integrating evidence from direct enzymatic N-glycan remodeling and indirect glycan-processing models, this review offers a novel perspective on glycan-mediated microbial-host interactions, highlighting how targeted modulation of these processes may advance therapeutic strategies against infectious diseases.