Recently found association linking viral infections to neurodegenerative diseases has raised concerns about unknown mechanisms in the communication between the respiratory and central nervous systems . We hypothesized that extracellular vesicles (EVs) can transfer viral signals to microglia, triggering the upregulation of pro-inflammatory cytokines by activating inflammasome-related pathways. In this study, we investigate the role of EVs released from virus mimetic poly I:C-infected human airway epithelial cells in modulating microglial immune responses. EVs were isolated from poly I:C-primed cultured human airway epithelial cells medium using polymer precipitation and characterized by markers (Luminex), size (NTA), and morphology (cryo-TEM). Fluorescent markers were used to track EVs, and the transfer of viral material was monitored using dihydrorhodamine-conjugated poly I:C. Microglia were treated with EVs to measure inflammasome activation using a luminescent assay for caspase-1. The expression of pro-inflammatory cytokines was assessed using RT-PCR, while protein expression was measured with Luminex Immunoassay. Statistical analysis was performed using GraphPad Prism. Results indicated that EVs from infected airway epithelial cells were mostly 120-140 nm in diameter, had a lipid bilayer, showed markers of endosomal origin, transferred viral material and were internalized by microglia within 2 hours. The treatment of microglia with virus-primed EVs triggered the activation of caspase-1, linked with the formation of NLRP3 inflammasome, resulting in IL-18 and IL1β secretion, and significantly increased IL6, IL8 and TNFα gene and protein expression. Findings suggest that EVs released from poly I:C-treated human airway epithelial cells can transfer viral signals to microglia, leading to neuroinflammatory responses.