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The Citrobacter rodentium type III secretion system effector EspO affects mucosal damage repair and antimicrobial responses
- Source :
- PLoS Pathogens, PLoS Pathogens, 2018, 14 (10), pp.e1007406. ⟨10.1371/journal.ppat.1007406⟩, PLoS Pathogens, Public Library of Science, 2018, 14 (10), pp.e1007406. ⟨10.1371/journal.ppat.1007406⟩, PLOS Pathogens, PLoS Pathogens, Vol 14, Iss 10, p e1007406 (2018)
- Publication Year :
- 2018
-
Abstract
- Infection with Citrobacter rodentium triggers robust tissue damage repair responses, manifested by secretion of IL-22, in the absence of which mice succumbed to the infection. Of the main hallmarks of C. rodentium infection are colonic crypt hyperplasia (CCH) and dysbiosis. In order to colonize the host and compete with the gut microbiota, C. rodentium employs a type III secretion system (T3SS) that injects effectors into colonic intestinal epithelial cells (IECs). Once injected, the effectors subvert processes involved in innate immune responses, cellular metabolism and oxygenation of the mucosa. Importantly, the identity of the effector/s triggering the tissue repair response is/are unknown. Here we report that the effector EspO ,an orthologue of OspE found in Shigella spp, affects proliferation of IECs 8 and 14 days post C. rodentium infection as well as secretion of IL-22 from colonic explants. While we observed no differences in the recruitment of group 3 innate lymphoid cells (ILC3s) and T cells, which are the main sources of IL-22 at the early and late stages of C. rodentium infection respectively, infection with ΔespO was characterized by diminished recruitment of sub-mucosal neutrophils, which coincided with lower abundance of Mmp9 and chemokines (e.g. S100a8/9) in IECs. Moreover, mice infected with ΔespO triggered significantly lesser nutritional immunity (e.g. calprotectin, Lcn2) and expression of antimicrobial peptides (Reg3β, Reg3γ) compared to mice infected with WT C. rodentium. This overlapped with a decrease in STAT3 phosphorylation in IECs. Importantly, while the reduced CCH and abundance of antimicrobial proteins during ΔespO infection did not affect C. rodentium colonization or the composition of commensal Proteobacteria, they had a subtle consequence on Firmicutes subpopulations. EspO is the first bacterial virulence factor that affects neutrophil recruitment and secretion of IL-22, as well as expression of antimicrobial and nutritional immunity proteins in IECs.<br />Author summary Citrobacter rodentium is a gold standard model to study pathogen-host-microbiome interactions. Two of the hallmarks of C. rodentium infection are colonic damage repair responses and colitis; symptoms that are shared with inflammatory bowel diseases in humans. The processes leading to tissue damage repair responses and the implicated bacterial virulence factors are still elusive. In this paper, we show that the C. rodentium type III secretion system effector EspO plays a major role in triggering damage healing responses, recruitment of neutrophils to the colonic villi, secretion of IL-22 from colonic explants and expression of IL-22 regulated genes in intestinal epithelial cells. This paper is the first to report a bacterial virulence factor that impacts on both intestinal epithelial cell proliferation and immune responses.
- Subjects :
- 0301 basic medicine
Pulmonology
Neutrophils
Physiology
Secretion Systems
Pathology and Laboratory Medicine
Biochemistry
Type three secretion system
Mice
White Blood Cells
Intestinal mucosa
Animal Cells
Microbial Physiology
Citrobacter rodentium
Type III Secretion Systems
Medicine and Health Sciences
Bacterial Physiology
Biology (General)
Intestinal Mucosa
Post-Translational Modification
Phosphorylation
Immune Response
Effector
Innate lymphoid cell
Enterobacteriaceae Infections
3. Good health
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Cell Processes
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Anatomy
Cellular Types
Pathogens
Research Article
[SDV.IMM] Life Sciences [q-bio]/Immunology
QH301-705.5
Colon
Virulence Factors
Immune Cells
030106 microbiology
Immunology
Biology
digestive system
Microbiology
03 medical and health sciences
Immune system
Virology
Tissue Repair
Genetics
Animals
Secretion
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Molecular Biology
Cell Proliferation
Innate immune system
Blood Cells
Biology and Life Sciences
Proteins
Bacteriology
Cell Biology
RC581-607
Immunity, Innate
Mice, Inbred C57BL
Gastrointestinal Tract
030104 developmental biology
Respiratory Infections
Parasitology
Immunologic diseases. Allergy
Physiological Processes
Digestive System
Antimicrobial Cationic Peptides
Subjects
Details
- ISSN :
- 15537374 and 15537366
- Volume :
- 14
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS pathogens
- Accession number :
- edsair.doi.dedup.....94559957ea05d953857a0706331e551d