The infection-exclusive proteome of murine extracellular vesicles defines Klebsiella pneumoniae-induced immune response signatures.

Abstract

Extracellular vesicles (EVs) are small, lipid bi-layered structures released from various cell types throughout the body. These structures are responsible for the delivery of proteins, compounds, and communication signals across spatial distances. EVs are highly important to diverse biological processes within mammalian systems, including roles in cellular maintenance and homeostasis of physiological conditions and response to infection, and they have the potential to serve as diagnostic hallmarks of infection. Despite these advances and promise, knowledge of the dynamics of EV production and composition during bacterial infection is limited. In this study, we characterize phenotypic traits and proteome remodeling of host EVs derived from murine models during a state of infection by the bacterial pathogen, Klebsiella pneumoniae, compared to an uninfected control. Phenotypic profiling defines consistent size, diameter, and number of EVs from samples across infectious states, whereas a closer look into molecular regulation at the protein level defines core and infection-exclusive proteomes. Within the core proteome (i.e., protein detection common between plasma from uninfected vs. infected samples) clustering based on infectious state was observed and significant increase (p < 0.01) in fibrinogen production upon infection were reported. Conversely, assessment of the infection-exclusive EV proteome supported detection of EVs by Gene Ontology Cellular Component classification revealed an enrichment of proteins associated with blood microparticles, membrane-bound, and the extracellular region, and highlighted the production of immune-associated proteins classified by Gene Ontology Biological Processes. Overall, this study emphasizes complex reprogramming of the host EV proteome upon exposure to K. pneumoniae within a murine model of infection and proposes protein-level signatures indicative of bacterial infection.