Regulatory Mechanisms and Research Progress of Glycosylation Modification in the Transition from Latent Tuberculosis Infection to Active Tuberculosis

Latent tuberculosis infection (LTBI) is the main reservoir of active tuberculosis (ATB), yet the molecular mechanisms underlying its progression to active disease remain incompletely understood. As a key post-translational modification, glycosylation has recently emerged as an important regulator of this transition. This review systematically summarizes the types and regulatory mechanisms of glycosylation changes during the LTBI to ATB shift, offering a new perspective for the precise diagnosis and treatment of tuberculosis. In LTBI, immunoglobulin G (IgG) displays a protective glycan profile—high galactosylation, high sialylation, and low fucosylation—which maintains Fc gamma receptor (FcγR)-mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thereby sustaining immune homeostasis. In ATB, IgG undergoes a glycan shift: galactosylation and sialylation decrease while fucosylation increases, weakening antibody effector functions, lifting anti-inflammatory restraint, and tilting the immune response toward inflammatory damage. Concurrently, mycobacteria subvert host immunity through the mannose cap of mannosylated lipoarabinomannan (ManLAM) and sustain intracellular survival via O-mannosylation; together with altered host glycans, these changes synergistically disrupt granuloma homeostasis. Translationally, IgG glycan signatures show promise for distinguishing LTBI from ATB, identifying high-risk individuals, and monitoring treatment responses. Mycobacterial glycosyltransferase inhibitors also offer new anti-TB therapeutic avenues. In conclusion, glycosylation constitutes a core regulatory network linking host immunity and mycobacterial pathogenicity during the LTBI to ATB transition.