title: Tsr Chemoreceptor Interacts With IL-8 Provoking E. coli Transmigration Across Human Lung Epithelial Cells.
abstract: Bacterial colonization of epithelial surfaces and subsequent transmigration across the mucosal barrier are essential for the development of infection. We hypothesized that the methyl-accepting proteins (MCPs), known as chemoreceptors expressed on Escherichia coli (E. coli) bacterial surface, play an important role in mediating bacterial transmigration. We demonstrated a direct interaction between human interleukin-8 (IL-8) and Tsr receptor, a major MCP chemoreceptor. Stimulation of human lung epithelial cell monolayer with IL-8 resulted in increased E. coli adhesion and transmigration of the native strain (RP437) and a strain expressing only Tsr (UU2373), as compared to a strain (UU2599) with Tsr truncation. The augmented E. coli adhesion and migration was associated with a higher expression of carcinoembryonic antigen-related cell adhesion molecule 6 and production of inflammatory cytokines/chemokines, and a lower expression of the tight junction protein claudin-1 and the plasma membrane protein caveolin-1 in lung epithelial cells. An increased E. coli colonization and pulmonary cytokine production induced by the RP437 and UU2373 strains was attenuated in mice challenged with the UU2599 strain. Our results suggest a critical role of the E. coli Tsr chemoreceptor in mediating bacterial colonization and transmigration across human lung epithelium during development of pulmonary infections.
authors: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, and the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors: Bing
authors: B
authors: Han
authors: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, and the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors: Manshu
authors: M
authors: Li
authors: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, and the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors: Yonghao
authors: Y
authors: Xu
authors: Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors: Diana
authors: D
authors: Islam
authors: Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors: Julie
authors: J
authors: Khang
authors: Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors: Lorenzo
authors: L
authors: Del Sorbo
authors: Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.|Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Warren
authors: W
authors: Lee
authors: Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors: Katalin
authors: K
authors: Szaszi
authors: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, and the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors: Nanshan
authors: N
authors: Zhong
authors: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, and the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.|Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Arthur S
authors: AS
authors: Slutsky
authors: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, and the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors: Yimin
authors: Y
authors: Li
authors: The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, and the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.|Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada.|Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors: Haibo
authors: H
authors: Zhang
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D062445:Claudin-1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D030781:Organisms, Genetically Modified; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D017384:Sequence Deletion / Q000235:genetics; D057705:Transendothelial and Transepithelial Migration
chemical_list: D015703:Antigens, CD; D001426:Bacterial Proteins; C504117:CEACAM6 protein, human; D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D062445:Claudin-1; D016207:Cytokines; D058851:GPI-Linked Proteins; D018836:Inflammation Mediators; D016209:Interleukin-8; D008565:Membrane Proteins; C057635:Tsr protein, Bacteria