Journal Article

Intestinal organoids to model Salmonella infection and its impact on progenitors

Yan, Jin, The Second Xiangya Hospital of Central South University [Hunan, China], Infectiologie et Santé Publique (ISP) ; Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Central South University [Changsha], Vergnolle, Nathalie, Burlaud-Gaillard, Julien, Claverie, Coralie, Lacroix-Lamandé, Sonia, Pezier, Tiffany, Rolland, Corinne, Racaud-Sultan, Claire, Wiedemann, Agnès, Velge, Philippe, Edir, Anissa, Olivier, Michel, Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (PFME-Tours) ; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Institut de Recherche en Santé Digestive (IRSD) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse IN

2024

Overview

Abstract In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella . Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis.

• Publisher: Nature Publishing Group,HAL CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 631/1647 / 631/326 / 631/532 / Animal models / Animals / Caecum / Cell culture / Cell Differentiation / Cell lineage / Cell Proliferation / Disease Models, Animal / EGFR / Epidermal growth factor receptors / Epithelial cells / Epithelium / ErbB Receptors - genetics / ErbB Receptors - metabolism / Humanities and Social Sciences / Infections / Intestinal Mucosa - microbiology / Intestinal Mucosa - pathology / Intestine / Life Sciences / Mice / Mice, Inbred C57BL / multidisciplinary / Organoid / Organoids / Organoids - microbiology / Progenitor / Progenitor cells / Salmonella / Salmonella Infections - microbiology / Salmonella Infections - pathology / Salmonella Typhimurium / Salmonella typhimurium - pathogenicity / Salmonella typhimurium - physiology / Science / Science (multidisciplinary) / Stem cell / Stem cells / Stem Cells - metabolism / Tumorigenesis