Back to Search
Start Over
Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection.
- Source :
-
Infection and immunity [Infect Immun] 2015 Sep; Vol. 83 (9), pp. 3342-54. Date of Electronic Publication: 2015 Jun 15. - Publication Year :
- 2015
-
Abstract
- The hallmarks of enteropathogenic Escherichia coli (EPEC) infection are formation of attaching and effacing (A/E) lesions on mucosal surfaces and actin-rich pedestals on cultured cells, both of which are dependent on the type III secretion system effector Tir. Following translocation into cultured cells and clustering by intimin, Tir Y474 is phosphorylated, leading to recruitment of Nck, activation of N-WASP, and actin polymerization via the Arp2/3 complex. A secondary, weak, actin polymerization pathway is triggered via an NPY motif (Y454). Importantly, Y454 and Y474 play no role in A/E lesion formation on mucosal surfaces following infection with the EPEC-like mouse pathogen Citrobacter rodentium. In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in C. rodentium colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to C. rodentium infection. We found that deletion of amino acids 382 to 462 or 478 to 547 had no impact on the ability of Tir to mediate A/E lesion formation, although deletion of amino acids 478 to 547 affected Tir translocation. Examination of enterocytes isolated from infected mice revealed that a C. rodentium strain expressing Tir&#95;Y451A/Y471A recruited significantly fewer neutrophils to the colon and triggered less colonic hyperplasia on day 14 postinfection than the wild-type strain. Consistently, enterocytes isolated from mice infected with C. rodentium expressing Tir&#95;Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to C. rodentium infection.<br /> (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Actins metabolism
Animals
Bacterial Proteins genetics
Enterobacteriaceae Infections metabolism
Female
Flow Cytometry
Mice
Mice, Inbred C57BL
Mutagenesis, Site-Directed
Reverse Transcriptase Polymerase Chain Reaction
Swiss 3T3 Cells
Bacterial Proteins metabolism
Bacterial Secretion Systems physiology
Chemokine CXCL1 biosynthesis
Citrobacter rodentium
Enterobacteriaceae Infections immunology
Enterocytes metabolism
Neutrophil Infiltration physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 83
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 26077760
- Full Text :
- https://doi.org/10.1128/IAI.00291-15