Uptake of Tropheryma whipplei by Intestinal Epithelia
Archivos
Fecha
2023-04
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
MDPI
Nombre de Curso
Licencia CC
CC BY 4.0 DEED
Attribution 4.0 International
Licencia CC
https://creativecommons.org/licenses/by/4.0/
Resumen
Background: Tropheryma whipplei (TW) can cause different pathologies, e.g., Whipple’s disease and transient gastroenteritis. The mechanism by which the bacteria pass the intestinal epithelial barrier, and the mechanism of TW-induced gastroenteritis are currently unknown. Methods: Using ex vivo disease models comprising human duodenal mucosa exposed to TW in Ussing chambers, various intestinal epithelial cell (IEC) cultures exposed to TW and a macrophage/IEC coculture model served to characterize endocytic uptake mechanisms and barrier function. Results: TW exposed ex vivo to human small intestinal mucosae is capable of autonomously entering IECs, thereby invading the mucosa. Using dominant-negative mutants, TW uptake was shown to be dynamin- and caveolin-dependent but independent of clathrin-mediated endocytosis. Complementary inhibitor experiments suggested a role for the activation of the Ras/Rac1 pathway and actin polymerization. TW-invaded IECs underwent apoptosis, thereby causing an epithelial barrier defect, and were subsequently subject to phagocytosis by macrophages. Conclusions: TW enters epithelia via an actin-, dynamin-, caveolin-, and Ras-Rac1-dependent endocytosis mechanism and consecutively causes IEC apoptosis primarily in IECs invaded by multiple TW bacteria. This results in a barrier leak. Moreover, we propose that TW-packed IECs can be subject to phagocytic uptake by macrophages, thereby opening a potential entry point of TW into intestinal macrophages.
Notas
Indexación: Scopus.
Palabras clave
Apoptosis, Barrier function, Caveolin, Endocytosis, Gastroenteritis, Invasion, Tropheryma whipplei, Ussing chamber, Whipple’s disease
Citación
International Journal of Molecular Sciences, Open Access, Volume 24, Issue 7April 2023 Article number 6197
DOI
10.3390/ijms24076197