Revisiting tuberculosis through the Mtb and host cell extracellular vesicles

Abstract

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide, with complex and incompletely elucidated pathological mechanisms underlying its recalcitrance to cure. In recent years, the pivotal role of extracellular vesicles (EVs) in host-pathogen interactions has garnered increasing attention. This review systematically summarizes the multiple roles of Mycobacterium tuberculosis (Mtb)-derived EVs (Mtb EVs) and host cell-derived EVs (HC EVs) in the pathogenesis and progression of TB. Mtb EVs are enriched in virulence factors such as lipoproteins and lipoarabinomannan (LAM), contributing to the chronicity of TB by regulating immunosuppression, promoting bacterial dissemination, and enhancing environmental adaptation. In contrast, HC EVs - including exosomes, microvesicles, and apoptotic bodies - are hijacked by Mtb. Through the delivery of specific microRNAs (miRNAs), proteins, and other molecules, these distinct EVs subtypes reshape the host immune microenvironment, inhibit autophagy and apoptosis, and facilitate the persistent survival of bacteria, with exosomal miRNAs playing a particularly prominent role in immune suppression and metabolic reprogramming. Meanwhile, EVs also play crucial roles in anti-TB immune defense, such as activating macrophage inflammatory responses and promoting dendritic cell maturation and T-cell activation. Additionally, this review summarizes the broad application prospects of EVs in the development of novel TB vaccines, screening of diagnostic biomarkers, and design of targeted therapeutic strategies. It also highlights the current challenges in EVs subpopulation isolation, mechanistic dissection, and clinical translation, providing new perspectives for the precise prevention and control of TB in the future.