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Formyl peptide receptor 2 orchestrates mucosal protection against Citrobacter rodentium infection

Journal article
Authors Sinan Sharba
Vignes Venkatakrishnan
Médea Padra
Malene Winther
Michael Gabl
Martina Sundqvist
J. Wang
Huamei Forsman
Sara K. Lindén
Published in Virulence
Volume 10
Issue 1
Pages 610-624
ISSN 2150-5594
Publication year 2019
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 610-624
Language en
Links dx.doi.org/10.1080/21505594.2019.16...
Keywords Citrobacter rodentium, colitis, enteropathogenic Escherichia coli, Fpr2, Mucin, mucus, eotaxin, formylpeptide receptor, formylpeptide receptor 2, galactosamine, gamma interferon, glycan, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, interleukin 10, interleukin 12, interleukin 13, interleukin 17, interleukin 1alpha, interleukin 1beta, interleukin 2, interleukin 4, interleukin 5, interleukin 6, macrophage inflammatory protein 1alpha, macrophage inflammatory protein 1beta, monocyte chemotactic protein 1, n acetylglucosamine, n acetylneuraminic acid, n glycoloylneuraminic acid, RANTES, tumor necrosis factor, unclassified drug, animal cell, animal experiment, animal model, animal tissue, bacterial colonization, bacterial growth, bacterial infection, bacterial translocation, bacterium culture, cell infiltration, cell junction, Citrobacter rodentium infection, colitis score, colon epithelium, colony forming unit, controlled study, cytokine response, diagnostic procedure, electrospray mass spectrometry, exocytosis, feces microflora, fluorescence microscopy, glycosylation, histology, HT-29-MTX cell line, human, human cell, immunofluorescence test, intestine crypt, intestine mucosa, liquid chromatography-mass spectrometry, male, mechanical stimulation, microbial morphology, mouse, neutrophil count, nonhuman, periodic acid Schiff stain, protein expression, sialylation, stomach protection
Subject categories Medical cell biology

Abstract

Citrobacter rodentium is an attaching and effacing intestinal murine pathogen which shares similar virulence strategies with the human pathogens enteropathogenic- and enterohemorrhagic Escherichia coli to infect their host. C. rodentium is spontaneously cleared by healthy wild-type (WT) mice whereas mice lacking Muc2 or specific immune regulatory genes demonstrate an impaired ability to combat the pathogen. Here we demonstrate that apical formyl peptide receptor 2 (Fpr2) expression increases in colonic epithelial cells during C. rodentium infection. Using a conventional inoculum dose of C. rodentium, both WT and Fpr2−/− mice were infected and displayed similar signs of disease, although Fpr2−/− mice recovered more slowly than WT mice. However, Fpr2−/− mice exhibited increased susceptibility to C. rodentium colonization in response to low dose infection: 100% of the Fpr2−/− and 30% of the WT mice became colonized and Fpr2−/− mice developed more severe colitis and more C. rodentium were in contact with the colonic epithelial cells. In line with the larger amount of C. rodentium detected in the spleen in Fpr2−/− mice, more C. rodentium and enteropathogenic Escherichia coli translocated across an in vitro mucosal surface to the basolateral compartment following FPR2 inhibitor treatment. Fpr2−/− mice also lacked the striated inner mucus layer that was present in WT mice. Fpr2−/− mice had decreased mucus production and different mucin O-glycosylation in the colon compared to WT mice, which may contribute to their defect inner mucus layer. Thus, Fpr2 contributes to protection against infection and influence mucus production, secretion and organization. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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