Citrobacter rodentium infection induces persistent molecular changes and interferon gamma-dependent major histocompatibility complex class II expression in the colonic epithelium
File(s)
Published version
Author(s)
Mullineaux Sanders, Caroline
Kozik, Zuzanna
Sanchez Garrido, Julia
Hopkins, Eve GD
Choudhary, Jyoti S
Type
Journal Article
Abstract
Most studies of infections at mucosal surfaces have focused on the acute phase of the disease. Consequently, little is known about the molecular processes that underpin tissue recovery and the long-term consequences postinfection. Here, we conducted temporal deep quantitative proteomic analysis of colonic intestinal epithelial cells (cIECs) from mice infected with the natural mouse pathogen Citrobacter rodentium over time points corresponding to the late steady-state phase (10 days postinfection [DPI]), the clearance phase (13 to 20 DPI), and 4 weeks after the pathogen has been cleared (48 DPI). C. rodentium, which relies on a type III secretion system to infect, is used to model infections with enteropathogenic and enterohemorrhagic Escherichia coli. We observe a strong upregulation of inflammatory signaling and nutritional immunity responses during the clearance phase of the infection. Despite morphological tissue recovery, chromogranin B (ChgB)-positive endocrine cells remained significantly below baseline levels at 48 DPI. In contrast, we observed an increased abundance of proteins involved in antigen processing and presentation 4 weeks after pathogen clearance. In particular, long-term changes were characterized by a persistent interferon gamma (IFN-γ) response and the expression of major histocompatibility complex class II (MHCII) molecules in 60% of the EpCAM+ cIECs, which were not seen in Ifnγ−/− mice. Nonetheless, both wild-type and Ifnγ−/− mice mounted similar systemic and colonic IgG responses to C. rodentium and were equally protected from rechallenge, suggesting that cIEC MHCII is not necessary for protective immunity against C. rodentium.
Date Issued
2022-02-01
Date Acceptance
2022-01-05
Citation
mBio, 2022, 13 (1), pp.1-18
ISSN
2150-7511
Publisher
American Society for Microbiology
Start Page
1
End Page
18
Journal / Book Title
mBio
Volume
13
Issue
1
Copyright Statement
© 2022 Mullineaux-Sanders et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Sponsor
Wellcome Trust
Medical Research Council (MRC)
Identifier
https://journals.asm.org/doi/full/10.1128/mbio.03233-21
Grant Number
107057/Z/15/Z
MR/R020671/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Citrobacter rodentium
enteric infection
antigen presentation
HOST-DEFENSE
STEM-CELLS
VIRULENCE
PATHOGEN
Citrobacter rodentium
antigen presentation
enteric infection
0605 Microbiology
Publication Status
Published
Date Publish Online
2022-02-01