Viruso mimetiku Poli I:C veikiamų kvėpavimo takų egzosomų reikšmė mikroglijos ląstelių aktyvinimui / ; The effect of virus mimetic Poly I:C-primed airway exosomes on microglial cell activation.

One of the most common infectious diseases is viral infections of the upper respiratory tract. Usually, such infections are localized, however some of the factors, which cause infections might be transmitted to more remote locations by extracellular communication. The one of the best studied way of extracellular communication is nano-sized extracellular vesicles – exosomes. They are important for the exchange of substances between cells, the removal of unnecessary proteins or other molecules. Exosomes from virus-infected cells can carry pro-inflammatory molecules or even particles of the virus itself. It is known that exosomes can cross the blood-brain barrier. Because the upper respiratory tract is located very close to the brain, it is likely that virus-primed cell exosomes can transfer inflammatory factors to the brain and thus contribute to the initiation of neuroinflammatory processes. The most important immune response cells in the brain are microglia. Therefore, most likely, that those cells should be affected first of exosomes from virus-primed cells. However, the effect of virus-primed upper respiratory tract cell exosomes on microglia have not been studied yet. The aim of this project – to investigate the effect of virus mimetic poly I:C-primed airway exosomes on human microglial cell activation. In this project, exosomes were isolated from poly I:C-primed human bronchial epithelial cell culture medium and were characterized by particle size and specific exosomes markers. It was determined that the exosomes are internalized by microglial cells after 2 hours. It was established that the mitochondrial function of microglial cells is inhibited in the environment of virus-primed exosomes, and the energetic phenotype of the cells is redistributed towards less mitochondrial and more glycolytic. There is also an increase in the production of intracellular and mitochondrial reactive oxygen species and caspase-1 activity, indicating an activated state of microglia after exposure to viral sequence-stimulated ...