4.7 Article

Inside-out chicken enteroids with leukocyte component as a model to study host-pathogen interactions

Journal

COMMUNICATIONS BIOLOGY
Volume 4, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s42003-021-01901-z

Keywords

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Funding

  1. iCase studentship from the Biotechnology and Biological Sciences Research Council (BBSRC)
  2. MSD Animal Health [BB/MO14819]
  3. BBSRC [BBS/E/D/10002071, BBS/E/D/20002173]
  4. BBSRC [BBS/E/D/20002173, BBS/E/D/10002071] Funding Source: UKRI

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Researchers have developed complex 3D chicken enteroids that mimic intestinal organization, allowing for investigation of intestinal cell biology and host-pathogen interactions. These enteroids can develop optimally in suspension and have successfully been infected with Salmonella Typhimurium, influenza A virus, and Eimeria tenella without the need for micro-injection, providing a comprehensive model for exploring epithelial and leukocyte interactions in host-pathogen, food science, and pharmaceutical research.
Mammalian three-dimensional (3D) enteroids mirror in vivo intestinal organisation and are powerful tools to investigate intestinal cell biology and host-pathogen interactions. We have developed complex multilobulated 3D chicken enteroids from intestinal embryonic villi and adult crypts. These avian enteroids develop optimally in suspension without the structural support required to produce mammalian enteroids, resulting in an inside-out enteroid conformation with media-facing apical brush borders. Histological and transcriptional analyses show these enteroids comprise of differentiated intestinal epithelial cells bound by cell-cell junctions, and notably, include intraepithelial leukocytes and an inner core of lamina propria leukocytes. The advantageous polarisation of these enteroids has enabled infection of the epithelial apical surface with Salmonella Typhimurium, influenza A virus and Eimeria tenella without the need for micro-injection. We have created a comprehensive model of the chicken intestine which has the potential to explore epithelial and leukocyte interactions and responses in host-pathogen, food science and pharmaceutical research.

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