Altmetric

Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease

File Description SizeFormat 
cmi.13126.pdfPublished version18.36 MBAdobe PDFView/Open
Title: Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease
Authors: Carson, D
Barry, R
Eve GD, H
Roumeliotis, T
García-Weber, D
Mullineaux Sanders, C
Elinav, E
Arrieumerlou, C
Choudhary, J
Frankel, G
Item Type: Journal Article
Abstract: The mouse pathogen Citrobacter rodentium is used to model infections with enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC). Pathogenesis is commonly modelled in mice developing mild disease (e.g., C57BL/6). However, little is known about host responses in mice exhibiting severe colitis (e.g., C3H/HeN), which arguably provide a more clinically relevant model for human paediatric enteric infection. Infection of C3H/HeN mice with C. rodentium results in rapid colonic colonisation, coinciding with induction of key inflammatory signatures and colonic crypt hyperplasia. Infection also induces dramatic changes to bioenergetics in intestinal epithelial cells, with transition from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and higher abundance of SGLT4, LDHA, and MCT4. Concomitantly, mitochondrial proteins involved in the TCA cycle and OXPHOS were in lower abundance. Similar to observations in C57BL/6 mice, we detected simultaneous activation of cholesterol biogenesis, import, and efflux. Distinctly, however, the pattern recognition receptors NLRP3 and ALPK1 were specifically induced in C3H/HeN. Using cell‐based assays revealed that C. rodentium activates the ALPK1/TIFA axis, which is dependent on the ADP‐heptose biosynthesis pathway but independent of the Type III secretion system. This study reveals for the first time the unfolding intestinal epithelial cells' responses during severe infectious colitis, which resemble EPEC human infections.
Issue Date: Jan-2020
Date of Acceptance: 26-Sep-2019
URI: http://hdl.handle.net/10044/1/74359
DOI: 10.1111/cmi.13126
ISSN: 1462-5814
Publisher: Wiley
Start Page: 1
End Page: 17
Journal / Book Title: Cellular Microbiology
Volume: 22
Issue: 1
Copyright Statement: © 2019 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/R020671/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Microbiology
Citrobacter rodentium
immunology
infection
metabolic processes
microbial-cell interaction
NF-KAPPA-B
QUANTITATIVE TRAIT LOCUS
NLRP3 INFLAMMASOME
STEM-CELLS
ACTIVATION
COLITIS
EXPRESSION
INTERLEUKIN-22
SUSCEPTIBILITY
CHOLESTEROL
Citrobacter rodentium
immunology
infection
metabolic processes
microbial-cell interaction
0605 Microbiology
1108 Medical Microbiology
Microbiology
Publication Status: Published
Article Number: ARTN e13126
Online Publication Date: 2019-10-14
Appears in Collections:Faculty of Natural Sciences



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons