Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers

Many pathogens use M cells to access the underlying Peyer’s patches and spread to systemic sites via the lymph as demonstrated by ligated loop murine intestinal models. However, the study of interactions between M cells and microbial pathogens has stalled due to the lack of cell culture systems. To...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alyssa C. Fasciano, Gaya S. Dasanayake, Mary K. Estes, Nicholas C. Zachos, David T. Breault, Ralph R. Isberg, Shumin Tan, Joan Mecsas
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	m cell yersinia pseudotuberculosis human ileal enteroid polarized epithelial transcytosis organoid cell extrusion type three secretion system yope yoph Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/ffce43ceacb54f31bd1a2c82625cbc39
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ffce43ceacb54f31bd1a2c82625cbc39
record_format	dspace
spelling	oai:doaj.org-article:ffce43ceacb54f31bd1a2c82625cbc392021-11-26T11:19:48ZYersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers1949-09761949-098410.1080/19490976.2021.1988390https://doaj.org/article/ffce43ceacb54f31bd1a2c82625cbc392021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1988390https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Many pathogens use M cells to access the underlying Peyer’s patches and spread to systemic sites via the lymph as demonstrated by ligated loop murine intestinal models. However, the study of interactions between M cells and microbial pathogens has stalled due to the lack of cell culture systems. To overcome this obstacle, we use human ileal enteroid-derived monolayers containing five intestinal cell types including M cells to study the interactions between the enteric pathogen, Yersinia pseudotuberculosis (Yptb), and M cells. The Yptb type three secretion system (T3SS) effector Yops inhibit host defenses including phagocytosis and are critical for colonization of the intestine and Peyer’s patches. Therefore, it is not understood how Yptb traverses through M cells to breach the epithelium. By growing Yptb under two physiological conditions that mimic the early infectious stage (low T3SS-expression) or host-adapted stage (high T3SS-expression), we found that large numbers of Yptb specifically associated with M cells, recapitulating murine studies. Transcytosis through M cells was significantly higher by Yptb expressing low levels of T3SS, because YopE and YopH prevented Yptb uptake. YopE also caused M cells to extrude from the epithelium without inducing cell-death or disrupting monolayer integrity. Sequential infection with early infectious stage Yptb reduced host-adapted Yptb association with M cells. These data underscore the strength of enteroids as a model by discovering that Yops impede M cell function, indicating that early infectious stage Yptb more effectively penetrates M cells while the host may defend against M cell penetration of host-adapted Yptb.Alyssa C. FascianoGaya S. DasanayakeMary K. EstesNicholas C. ZachosDavid T. BreaultRalph R. IsbergShumin TanJoan MecsasTaylor & Francis Grouparticlem cellyersinia pseudotuberculosishuman ileal enteroidpolarized epithelialtranscytosisorganoidcell extrusiontype three secretion systemyopeyophDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	m cell yersinia pseudotuberculosis human ileal enteroid polarized epithelial transcytosis organoid cell extrusion type three secretion system yope yoph Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	m cell yersinia pseudotuberculosis human ileal enteroid polarized epithelial transcytosis organoid cell extrusion type three secretion system yope yoph Diseases of the digestive system. Gastroenterology RC799-869 Alyssa C. Fasciano Gaya S. Dasanayake Mary K. Estes Nicholas C. Zachos David T. Breault Ralph R. Isberg Shumin Tan Joan Mecsas Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
description	Many pathogens use M cells to access the underlying Peyer’s patches and spread to systemic sites via the lymph as demonstrated by ligated loop murine intestinal models. However, the study of interactions between M cells and microbial pathogens has stalled due to the lack of cell culture systems. To overcome this obstacle, we use human ileal enteroid-derived monolayers containing five intestinal cell types including M cells to study the interactions between the enteric pathogen, Yersinia pseudotuberculosis (Yptb), and M cells. The Yptb type three secretion system (T3SS) effector Yops inhibit host defenses including phagocytosis and are critical for colonization of the intestine and Peyer’s patches. Therefore, it is not understood how Yptb traverses through M cells to breach the epithelium. By growing Yptb under two physiological conditions that mimic the early infectious stage (low T3SS-expression) or host-adapted stage (high T3SS-expression), we found that large numbers of Yptb specifically associated with M cells, recapitulating murine studies. Transcytosis through M cells was significantly higher by Yptb expressing low levels of T3SS, because YopE and YopH prevented Yptb uptake. YopE also caused M cells to extrude from the epithelium without inducing cell-death or disrupting monolayer integrity. Sequential infection with early infectious stage Yptb reduced host-adapted Yptb association with M cells. These data underscore the strength of enteroids as a model by discovering that Yops impede M cell function, indicating that early infectious stage Yptb more effectively penetrates M cells while the host may defend against M cell penetration of host-adapted Yptb.
format	article
author	Alyssa C. Fasciano Gaya S. Dasanayake Mary K. Estes Nicholas C. Zachos David T. Breault Ralph R. Isberg Shumin Tan Joan Mecsas
author_facet	Alyssa C. Fasciano Gaya S. Dasanayake Mary K. Estes Nicholas C. Zachos David T. Breault Ralph R. Isberg Shumin Tan Joan Mecsas
author_sort	Alyssa C. Fasciano
title	Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
title_short	Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
title_full	Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
title_fullStr	Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
title_full_unstemmed	Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers
title_sort	yersinia pseudotuberculosis yope prevents uptake by m cells and instigates m cell extrusion in human ileal enteroid-derived monolayers
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/ffce43ceacb54f31bd1a2c82625cbc39
work_keys_str_mv	AT alyssacfasciano yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers AT gayasdasanayake yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers AT marykestes yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers AT nicholasczachos yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers AT davidtbreault yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers AT ralphrisberg yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers AT shumintan yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers AT joanmecsas yersiniapseudotuberculosisyopepreventsuptakebymcellsandinstigatesmcellextrusioninhumanilealenteroidderivedmonolayers
_version_	1718409511857815552

Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers

Ejemplares similares