Investigation of the Roles of Exosomes Generated by Intestinal Organoids upon Enteroviral Infections in Pathogenesis

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

As the organ with the biggest mucosa surface, gastrointestinal (GI) tract is equipped with highly specialized immune system, which comprises a single layer of intestinal epithelial cells that functions as physical barrier, and various immune cells. However, some pathogens can sneak through the intestinal lining and dodge the immune system to invade the organism. Compared to other enteric viral pathogens, enteroviruses are able to invade other organs such as the central nervous system from GI tract. Thus, enteroviruses have been deemed as the leading cause for viral meningitis. However, the pathogenesis about enteroviruses has not been cleared yet. The limitations of enteric viral pathogen studies are the lack of appropriate cell and animal models. Benefit from recent advances in stem cell biology, the method about generation of human intestinal organoids (HIOs) from stem cells has been established. We have applied the differentiated intestinal organoids to investigate the influences of enteroviral infection and found that EV71 was able to exit the cells without triggering apoptosis. Furthermore, we observed that EV71 induced intestinal organoids to secrete exosomes, which could establish infection in other cells.Previous studies indicated that exosomes that released by virus infected cells may facilitate virus spreading or modulate immune responses of recipient cells. Exosomes are microvesicles released from various cell types. These extracellular vesicles contain sorted components including proteins, lipids, and nucleic acids, which mediate as messengers for cell-to-cell communication and hence play a role in physiology and pathology. The cargo of exosomes depends on types of cells and stimuli. Therefore, using an appropriate cell model is important for exosome study. Based on our preliminary results, we anticipate that enterovirus infection can trigger intestinal epithelial cells to secrete exosomes to facilitate virus spreading and hence we propose this study to investigate the exerted effects of exosomes and the mechanisms underlying the interactions of virus and exosome machinery. The specific aims of this study are as follows: (1) To investigate the roles of intestinal epithelial cells released exosomes in pathogenesis of enterovirus infection; (2) To characterize the non-coding RNA and protein profiles of exosomes; (3) To investigate the mechanisms associated with enterovirus-induced modification of exosomal machinery.

Project IDs

Project ID:PC10708-0738
External Project ID:MOST107-2320-B182-008
StatusFinished
Effective start/end date01/08/1831/07/19

Keywords

  • enteroviruses
  • intestinal organoid
  • exosome
  • pathogenesis
  • transmission

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