Exosomes Released during Infection with Burkholderia thailandensis Play a Protective Role for the Host through Stimulation of Innate Immune Responses
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Authors
Hobbs, Heather
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Abstract
Exosomes are extracellular vesicles that play a central role in intercellular communication. They have recently attracted much attention as their significant function in a variety of disease, including infectious diseases, has become better understood. However, there are significant gaps in our knowledge regarding how exosomes derived from an infectious origin (EXi) can alter host innate immunity. Using our model of purifying exosomes from Burkholderia pseudomallei (Bp) infected cells, we aimed to better understand the role host exosomes play in the pathogenesis of Bp, a Category B priority pathogen that possess significant risk to public health and for which we currently have no effective countermeasures. We have shown that EXi induce human monocytes to differentiate into macrophage-like cells and stimulate the release of IL-2, IL-6, and TNF-α. Additionally, we have demonstrated that EXi promote increased bacterial clearance in treated naïve monocytes, and experiments are under way to elucidate the exact mechanisms. We have also analyzed the protein complements of the EXi and EXu by mass spectrometry analysis. Collectively, our data support a model in which the EXi prime local and distal naïve cells to mount a more effective response against Bp. These findings provide insights into a previously unexplored aspect of host response to infection, which can aid in future development of novel vaccines or therapeutics against bacterial pathogens.
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This thesis has been embargoed for 2 years and will not be available until July 2020 at the earliest.
Keywords
Exosomes, Burkholderia pseudomallei, Innate immune response, Extracellular vesicles, Bacterial dissemination, Burkholderia thailandensis