Presenting Author: Puja Kumari
, Postdoc at UConn Hlth.
Abstract:
Intracellular immune surveillance for systemic microbial components during homeostasis and infections governs host physiology and immunity. However, a long-standing question is how circulating microbial ligands become accessible to intracellular receptors. Here, we show a role for host-derived extracellular vesicles (EVs) in this process; human and murine plasma- and cell culture-derived EVs have an intrinsic capacity to bind bacterial lipopolysaccharide (LPS). Remarkably, circulating host EVs capture blood-borne LPS in vivo, and the LPS-laden EVs confer cytosolic access for LPS, triggering noncanonical inflammasome activation of GSDMD and pyroptosis. Mechanistically, the interaction between EV lipid bilayer and LPS’ lipid A underlies EV capture of LPS. Furthermore, the intracellular transfer of LPS by EVs is mediated by CD14-dependent receptor-mediated endocytosis. Overall, this study demonstrates that EVs capture and escort systemic LPS to the cytosol licensing inflammasome responses, uncovering EVs as a previously unrecognized link between systemic pathogen-associated molecular pattern (PAMPs) and intracellular immune surveillance.
Unveiling the immune surveillance role of extracellular vesicles
Category
Poster and Podium (Block Symposium)
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Date: May 6 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1