Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection

ABSTRACT We used the mouse attaching and effacing (A/E) pathogen Citrobacter rodentium, which models the human A/E pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli (EPEC and EHEC), to temporally resolve intestinal epithelial cell (IEC) responses and changes to the microbiome...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Eve G. D. Hopkins, Theodoros I. Roumeliotis, Caroline Mullineaux-Sanders, Jyoti S. Choudhary, Gad Frankel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	cholesterol homeostasis Citrobacter rodentium host response to infection intestinal epithelial cells the microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a67581a0f3b94343866cb0b1dbcd1ec0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a67581a0f3b94343866cb0b1dbcd1ec0
record_format	dspace
spelling	oai:doaj.org-article:a67581a0f3b94343866cb0b1dbcd1ec02021-11-15T15:55:24ZIntestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection10.1128/mBio.00062-192150-7511https://doaj.org/article/a67581a0f3b94343866cb0b1dbcd1ec02019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00062-19https://doaj.org/toc/2150-7511ABSTRACT We used the mouse attaching and effacing (A/E) pathogen Citrobacter rodentium, which models the human A/E pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli (EPEC and EHEC), to temporally resolve intestinal epithelial cell (IEC) responses and changes to the microbiome during in vivo infection. We found the host to be unresponsive during the first 3 days postinfection (DPI), when C. rodentium resides in the caecum. In contrast, at 4 DPI, the day of colonic colonization, despite only sporadic adhesion to the apex of the crypt, we observed robust upregulation of cell cycle and DNA repair processes, which were associated with expansion of the crypt Ki67-positive replicative zone, and downregulation of multiple metabolic processes (including the tricarboxylic acid [TCA] cycle and oxidative phosphorylation). Moreover, we observed dramatic depletion of goblet and deep crypt secretory cells and an atypical regulation of cholesterol homeostasis in IECs during early infection, with simultaneous upregulation of cholesterol biogenesis (e.g., 3-hydroxy-3-methylglutaryl–coenzyme A reductase [Hmgcr]), import (e.g., low-density lipoprotein receptor [Ldlr]), and efflux (e.g., AbcA1). We also detected interleukin 22 (IL-22) responses in IECs (e.g., Reg3γ) on the day of colonic colonization, which occurred concomitantly with a bloom of commensal Enterobacteriaceae on the mucosal surface. These results unravel a new paradigm in host-pathogen-microbiome interactions, showing for the first time that sensing a small number of pathogenic bacteria triggers swift intrinsic changes to the IEC composition and function, in tandem with significant changes to the mucosa-associated microbiome, which parallel innate immune responses. IMPORTANCE The mouse pathogen C. rodentium is a widely used model for colonic infection and has been a major tool in fundamental discoveries in the fields of bacterial pathogenesis and mucosal immunology. Despite extensive studies probing acute C. rodentium infection, our understanding of the early stages preceding the infection climax remains relatively undetailed. To this end, we apply a multiomics approach to resolve temporal changes to the host and microbiome during early infection. Unexpectedly, we found immediate and dramatic responses occurring on the day of colonic infection, both in the host intestinal epithelial cells and in the microbiome. Our study suggests changes in cholesterol and carbon metabolism in epithelial cells are instantly induced upon pathogen detection in the colon, corresponding with a shift to primarily facultative anaerobes constituting the microbiome. This study contributes to our knowledge of disease pathogenesis and mechanisms of barrier regulation, which is required for development of novel therapeutics targeting the intestinal epithelium.Eve G. D. HopkinsTheodoros I. RoumeliotisCaroline Mullineaux-SandersJyoti S. ChoudharyGad FrankelAmerican Society for Microbiologyarticlecholesterol homeostasisCitrobacter rodentiumhost response to infectionintestinal epithelial cellsthe microbiomeMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cholesterol homeostasis Citrobacter rodentium host response to infection intestinal epithelial cells the microbiome Microbiology QR1-502
spellingShingle	cholesterol homeostasis Citrobacter rodentium host response to infection intestinal epithelial cells the microbiome Microbiology QR1-502 Eve G. D. Hopkins Theodoros I. Roumeliotis Caroline Mullineaux-Sanders Jyoti S. Choudhary Gad Frankel Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection
description	ABSTRACT We used the mouse attaching and effacing (A/E) pathogen Citrobacter rodentium, which models the human A/E pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli (EPEC and EHEC), to temporally resolve intestinal epithelial cell (IEC) responses and changes to the microbiome during in vivo infection. We found the host to be unresponsive during the first 3 days postinfection (DPI), when C. rodentium resides in the caecum. In contrast, at 4 DPI, the day of colonic colonization, despite only sporadic adhesion to the apex of the crypt, we observed robust upregulation of cell cycle and DNA repair processes, which were associated with expansion of the crypt Ki67-positive replicative zone, and downregulation of multiple metabolic processes (including the tricarboxylic acid [TCA] cycle and oxidative phosphorylation). Moreover, we observed dramatic depletion of goblet and deep crypt secretory cells and an atypical regulation of cholesterol homeostasis in IECs during early infection, with simultaneous upregulation of cholesterol biogenesis (e.g., 3-hydroxy-3-methylglutaryl–coenzyme A reductase [Hmgcr]), import (e.g., low-density lipoprotein receptor [Ldlr]), and efflux (e.g., AbcA1). We also detected interleukin 22 (IL-22) responses in IECs (e.g., Reg3γ) on the day of colonic colonization, which occurred concomitantly with a bloom of commensal Enterobacteriaceae on the mucosal surface. These results unravel a new paradigm in host-pathogen-microbiome interactions, showing for the first time that sensing a small number of pathogenic bacteria triggers swift intrinsic changes to the IEC composition and function, in tandem with significant changes to the mucosa-associated microbiome, which parallel innate immune responses. IMPORTANCE The mouse pathogen C. rodentium is a widely used model for colonic infection and has been a major tool in fundamental discoveries in the fields of bacterial pathogenesis and mucosal immunology. Despite extensive studies probing acute C. rodentium infection, our understanding of the early stages preceding the infection climax remains relatively undetailed. To this end, we apply a multiomics approach to resolve temporal changes to the host and microbiome during early infection. Unexpectedly, we found immediate and dramatic responses occurring on the day of colonic infection, both in the host intestinal epithelial cells and in the microbiome. Our study suggests changes in cholesterol and carbon metabolism in epithelial cells are instantly induced upon pathogen detection in the colon, corresponding with a shift to primarily facultative anaerobes constituting the microbiome. This study contributes to our knowledge of disease pathogenesis and mechanisms of barrier regulation, which is required for development of novel therapeutics targeting the intestinal epithelium.
format	article
author	Eve G. D. Hopkins Theodoros I. Roumeliotis Caroline Mullineaux-Sanders Jyoti S. Choudhary Gad Frankel
author_facet	Eve G. D. Hopkins Theodoros I. Roumeliotis Caroline Mullineaux-Sanders Jyoti S. Choudhary Gad Frankel
author_sort	Eve G. D. Hopkins
title	Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection
title_short	Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection
title_full	Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection
title_fullStr	Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection
title_full_unstemmed	Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection
title_sort	intestinal epithelial cells and the microbiome undergo swift reprogramming at the inception of colonic <named-content content-type="genus-species">citrobacter rodentium</named-content> infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/a67581a0f3b94343866cb0b1dbcd1ec0
work_keys_str_mv	AT evegdhopkins intestinalepithelialcellsandthemicrobiomeundergoswiftreprogrammingattheinceptionofcolonicnamedcontentcontenttypegenusspeciescitrobacterrodentiumnamedcontentinfection AT theodorosiroumeliotis intestinalepithelialcellsandthemicrobiomeundergoswiftreprogrammingattheinceptionofcolonicnamedcontentcontenttypegenusspeciescitrobacterrodentiumnamedcontentinfection AT carolinemullineauxsanders intestinalepithelialcellsandthemicrobiomeundergoswiftreprogrammingattheinceptionofcolonicnamedcontentcontenttypegenusspeciescitrobacterrodentiumnamedcontentinfection AT jyotischoudhary intestinalepithelialcellsandthemicrobiomeundergoswiftreprogrammingattheinceptionofcolonicnamedcontentcontenttypegenusspeciescitrobacterrodentiumnamedcontentinfection AT gadfrankel intestinalepithelialcellsandthemicrobiomeundergoswiftreprogrammingattheinceptionofcolonicnamedcontentcontenttypegenusspeciescitrobacterrodentiumnamedcontentinfection
_version_	1718427167099977728

Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic <named-content content-type="genus-species">Citrobacter rodentium</named-content> Infection

Ejemplares similares