Extracellular Vesicles Cargo in Modulating Microglia Functional Responses

SIMPLE SUMMARY: Extracellular vesicles (EVs) are considered a new additional mechanism of intercellular communication also in brain cells. Microglia are brain-resident immune cells that provided to immune surveillance and inflammatory responses in the central nervous system. The goal of this research is to investigate how EVs of brain, in particular if EVs isolated from microglia in response to LPS (Lipopolysaccharide) may have the ability to induce an inflammatory state in microglia. This study has showed that EVs with LPS cargo can activate microglia in a manner similar to that of LPS alone and that EVs derived from control cells cannot polarize microglia towards a pro-inflammatory state. The importance of this study is the demonstration that EVs produced in an inflammatory environment can exacerbate the inflammatory message by activating microglia, which may have a negative impact on all brain cells. ABSTRACT: Extracellular vesicles (EVs) represent a heterogeneous group of membranous structures derived from cells that are released by all cell types, including brain cells. EVs are now thought to be an additional mechanism of intercellular communication. Both under normal circumstances and following the addition of proinflammatory stimuli, microglia release EVs, but the contents of these two types of EVs are different. Microglia are considered the brain-resident immune cells that are involved in immune surveillance and inflammatory responses in the central nervous system. In this research, we have analyzed the effects of EVs isolated from microglia in response to LPS (Lipopolysaccharide) on microglia activation. The EVs produced as result of LPS stimulation, knows as EVs-LPS, were then used as stimuli on microglia BV2 resting cells in order to investigate their ability to induce microglia to polarize towards an inflammatory state. After EVs-LPS stimulation, we analyzed the change to BV2 cells’ morphology, proliferation, and migration, and investigated the expression and the release of pro-inflammatory cytokines. The encouraging findings of this study showed that EVs-LPS can activate microglia in a manner similar to that of LPS alone and that EVs derived from control cells cannot polarize microglia towards a pro-inflammatory state. This study has confirmed the critical role of EVs in communication and shown how EVs produced in an inflammatory environment can exacerbate the inflammatory process by activating microglia, which may have an impact on all brain cells.