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Figure 4. Translational applications of Mtb EVs and HC EVs in TB vaccines, diagnosis, and therapy. For vaccine development, both natural and engineered EVs strategies are employed: natural EVs from BCG-infected macrophages induce protective Th1 and memory T-cell responses, while engineered approaches - including ubiquitin-fusion-mediated antigen enrichment, biomimetic nanocarrier conjugation, and multi-epitope design - enhance antigen stability, immune activation, and scalability. As diagnostic tools, EVs serve as stable carriers of multi-omic biomarkers (host miRNAs, lncRNAs, Mtb-specific nucleic acids, proteins such as Ag85B, LAM, MPT64, and lipids) in accessible bodily fluids, enabling TB detection, differentiation of active from latent infection, discrimination between TB and other pulmonary diseases (e.g., lung cancer), and monitoring of treatment efficacy and drug resistance. For targeted therapy, EVs leverage their biocompatibility, low immunogenicity, and barrier-crossing ability as drug delivery vectors, with strategies including endogenous loading via parental cell engineering, exogenous loading of anti-TB drugs or immunomodulatory molecules, and surface modification to enhance targeting to infected cells, collectively improving therapeutic efficacy while reducing systemic toxicity. These EVs-based strategies collectively offer versatile translational solutions for advancing TB prevention, diagnosis, and treatment. Mtb: Mycobacterium tuberculosis; EVs: extracellular vesicles; Mtb EVs: Mycobacterium tuberculosis-derived extracellular vesicles; HC EVs: host cell-derived extracellular vesicles; TB: tuberculosis; BCG: Bacillus Calmette-Guérin; CFP: culture filtrate proteins; Th1: T helper type 1; DC: dendritic cell; RNA: ribonucleic acid; miRNA: microRNA; lncRNA: long non-coding RNA; Ag85B: antigen 85B; LAM: lipoarabinomannan; MPT64: Mycobacterium tuberculosis protein 64; AuNP: gold nanoparticle; EV-AuNP: extracellular vesicle-coated gold nanoparticle; BALF: bronchoalveolar lavage fluid; CSF: cerebrospinal fluid; ATB: active tuberculosis; LTBI: latent tuberculosis infection; MDR-TB: multidrug-resistant tuberculosis; ROS: reactive oxygen species; VC: vitamin C.