title: Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis.
abstract: Gut-associated inflammation plays a crucial role in the progression of colon cancer. Here, we identify a novel pathogen-host interaction that promotes gut inflammation and the development of colon cancer. We find that enteropathogenic bacteria-secreted particles (ET-BSPs) stimulate intestinal epithelium to produce IDENs (intestinal mucosa-derived exosome-like nanoparticles) containing elevated levels of sphingosine-1-phosphate, CCL20 and prostaglandin E2 (PGE2). CCL20 and PGE2 are required for the recruitment and proliferation, respectively, of Th17 cells, and these processes also involve the MyD88-mediated pathway. By influencing the recruitment and proliferation of Th17 cells in the intestine, IDENs promote colon cancer. We demonstrate the biological effect of sphingosine-1-phosphate contained in IDENs on tumour growth in spontaneous and transplanted colon cancer mouse models. These findings provide deeper insights into how host-microbe relationships are mediated by particles secreted from both bacterial and host cells.
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Anatomical Sciences and Neurobiology, University of Louisville, Kentucky 40202, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tseng
authors.affiliation: 1] James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA [2] The Departments of Medicine, Biochemistry and Molecular Genetics, and Pharmacology and Toxicology, University of Louisville, Kentucky 40202, USA.
authors.forename: Binks
authors.initials: B
authors.lastname: Wattenberg
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Nejat K
authors.initials: NK
authors.lastname: Egilmez
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: James
authors.initials: J
authors.lastname: Norris
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Haixun
authors.initials: H
authors.lastname: Guo
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Jun
authors.identifier: 000000032922422X
authors.initials: J
authors.lastname: Yan
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Bodduluri
authors.initials: B
authors.lastname: Haribabu
authors.affiliation: James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: 1] James Graham Brown Cancer Center, Department of Microbiology &Immunology, University of Louisville, Kentucky 40202, USA [2] Robley Rex VA Medical Center, Louisville, Kentucky 40206, USA.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D001441:Bacteroides fragilis / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D063646:Carcinogenesis / Q000276:immunology*; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000276:immunology*; D003110:Colonic Neoplasms / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D015232:Dinoprostone / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004755:Enterobacteriaceae / Q000276:immunology* / Q000378:metabolism; D055354:Exosomes / Q000276:immunology*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007249:Inflammation; D007413:Intestinal Mucosa / Q000276:immunology*; D008246:Lysophospholipids / Q000276:immunology*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C493447:CCL20 protein, mouse; D002273:Carcinogens; D054418:Chemokine CCL20; D008246:Lysophospholipids; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C060506:sphingosine 1-phosphate; D016264:Dextran Sulfate; D015232:Dinoprostone; D001397:Azoxymethane; D013110:Sphingosine