{"doi":"10.1128/iai.00291-15","title":"Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            The hallmarks of enteropathogenic\n            <jats:named-content content-type=\"genus-species\">Escherichia coli</jats:named-content>\n            (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\n            <jats:named-content content-type=\"genus-species\">Citrobacter rodentium</jats:named-content>\n            . In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            strain expressing Tir_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\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            expressing Tir_Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            infection.\n          </jats:p>","journal":"Infection and Immunity","year":2015,"id":613336,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1580058,"name":"Maryam Habibzay","orcid":null,"position":1,"is_corresponding":false},{"id":1580059,"name":"Izabela Glegola-Madejska","orcid":null,"position":2,"is_corresponding":false},{"id":1485102,"name":"Marianne Guenot","orcid":null,"position":3,"is_corresponding":false},{"id":492224,"name":"James W. Collins","orcid":"0000-0002-6396-2579","position":4,"is_corresponding":false},{"id":459688,"name":"Gad Frankel","orcid":"0000-0002-0046-1363","position":5,"is_corresponding":false},{"id":1580057,"name":"Valerie F. Crepin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            The hallmarks of enteropathogenic\n            <jats:named-content content-type=\"genus-species\">Escherichia coli</jats:named-content>\n            (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\n            <jats:named-content content-type=\"genus-species\">Citrobacter rodentium</jats:named-content>\n            . In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            strain expressing Tir_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\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            expressing Tir_Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to\n            <jats:named-content content-type=\"genus-species\">C. rodentium</jats:named-content>\n            infection.\n          </jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26077760","pmcid":"PMC4534649","openalex_id":"https://openalex.org/W2212304636","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"107057/Z/15/Z","title":null},{"funder_name":"Medical Research Council","grant_id":"MR/J006874/1","title":null},{"funder_name":"Medical Research Council","grant_id":"MR/K019007/1","title":null},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":7,"fwci":2.5464,"citation_percentile":0.88417618,"influential_citations":0,"citation_trend":[{"year":2016,"count":6},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":4},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://iai.asm.org/content/iai/83/9/3342.full.pdf","host_type":"journal"},{"url":"https://iai.asm.org/content/iai/83/9/3342.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/IAI.00291-15","host_type":"publisher"},{"url":"https://doi.org/10.1128/iai.00291-15","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26077760","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4534649","host_type":"repository"},{"url":"https://researchonline.lshtm.ac.uk/id/eprint/4646405/","host_type":"repository"}],"fields_of_study":["Escherichia coli research studies","Antibiotic Resistance in Bacteria","Probiotics and Fermented Foods","Actins","Animals","Bacterial Proteins","Bacterial Secretion Systems","Chemokine CXCL1","Citrobacter rodentium","Enterobacteriaceae Infections","Enterocytes","Female","Flow Cytometry","Mice","Mice, Inbred C57BL","Mutagenesis, Site-Directed","Neutrophil Infiltration","Reverse Transcriptase Polymerase Chain Reaction","Swiss 3T3 Cells"],"mesh_terms":["Actins","Animals","Bacterial Proteins","Enterobacteriaceae Infections","Female","Flow Cytometry","Mice, Inbred C57BL","Mutagenesis, Site-Directed","Reverse Transcriptase Polymerase Chain Reaction","Neutrophil Infiltration","Enterocytes","Swiss 3T3 Cells","Citrobacter rodentium","Mice","Chemokine CXCL1","Bacterial Secretion Systems"],"keywords":["Citrobacter rodentium","Biology","Enteropathogenic Escherichia coli","Intimin","Microbiology","CXCL1","Actin","Citrobacter","Effector","Secretion","Type three secretion system","Lesion","Immune system","Cell biology","Pathogen","Escherichia coli","Virulence","Enterobacteriaceae","Chemokine","Immunology","Pathology","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T07:41:05.340633Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}