Extracellular Vesicles From Mycoplasma gallisepticum: Modulators of Macrophage Activation and Virulence

Abstract Extracellular vesicles (EVs) mediate intercellular communication by transporting proteins. To investigate the pathogenesis of Mycoplasma gallisepticum, a major threat to the poultry industry, we isolated and characterized M. gallisepticum–produced EVs. Our study highlights the significant impact of M. gallisepticum–derived EVs on immune function and macrophage apoptosis, setting them apart from other M. gallisepticum metabolites. These EVs dose-dependently enhance M. gallisepticum adhesion and proliferation, simultaneously modulating Toll-like receptor 2 and interferon γ pathways and thereby inhibiting macrophage activation. A comprehensive protein analysis revealed 117 proteins in M. gallisepticum–derived EVs, including established virulence factors, such as GapA, CrmA, VlhA, and CrmB. Crucially, these EV-associated proteins significantly contribute to M. gallisepticum infection. Our findings advance our comprehension of M. gallisepticum pathogenesis, offering insights for preventive strategies and emphasizing the pivotal role of M. gallisepticum–derived EVs and their associated proteins. This research sheds light on the composition and crucial role of M. gallisepticum–derived EVs in M. gallisepticum pathogenesis, aiding our fight against M. gallisepticum infections.