Role of Exosomes During Mycobacterium Tuberculosis Infection: A Double-Edged Sword

Exosomes are nanoscale, double-membrane extracellular vesicles of endocytic origin that are released by diverse cell types under both physiological and pathological conditions. They have emerged as critical mediators of intercellular communication and immune regulation during homeostasis and infection. Accumulating evidence indicates that pathogen-infected mammalian cells actively secrete exosomes enriched with host- and pathogen-derived components, including proteins, lipids, DNA, and regulatory RNAs such as microRNA (miRNA) and circular RNA (circRNA). In the context of infection, exosomes exhibit dual and often opposing functions, contributing to both host defense and disease progression. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis and a leading cause of mortality from infectious diseases worldwide, has been shown to modulate exosome biogenesis and alter cargo composition in exosomes when secreted by macrophages. These exosomes carry mycobacterial antigens and immunomodulatory molecules that can influence host immune responses, thereby shaping disease outcomes. This review summarizes current insights into the biogenesis and functional roles of exosomes during Mtb infection, highlighting their contributions to host–pathogen interactions, immune modulation, and disease pathogenesis. We further discuss the potential of exosomes as biomarkers and therapeutic targets in tuberculosis, emphasizing their dual roles in mediating protective and detrimental effects.