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Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis

Author

Listed:
  • Zhongbin Deng

    (James Graham Brown Cancer Center, University of Louisville)

  • Jingyao Mu

    (James Graham Brown Cancer Center, University of Louisville)

  • Michael Tseng

    (University of Louisville)

  • Binks Wattenberg

    (James Graham Brown Cancer Center, University of Louisville
    Biochemistry and Molecular Genetics, and Pharmacology and Toxicology, University of Louisville)

  • Xiaoying Zhuang

    (James Graham Brown Cancer Center, University of Louisville)

  • Nejat K. Egilmez

    (James Graham Brown Cancer Center, University of Louisville)

  • Qilong Wang

    (James Graham Brown Cancer Center, University of Louisville)

  • Lifeng Zhang

    (James Graham Brown Cancer Center, University of Louisville)

  • James Norris

    (Medical University of South Carolina)

  • Haixun Guo

    (James Graham Brown Cancer Center, University of Louisville)

  • Jun Yan

    (James Graham Brown Cancer Center, University of Louisville)

  • Bodduluri Haribabu

    (James Graham Brown Cancer Center, University of Louisville)

  • Donald Miller

    (James Graham Brown Cancer Center, University of Louisville)

  • Huang-Ge Zhang

    (James Graham Brown Cancer Center, University of Louisville
    Robley Rex VA Medical Center)

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.

Suggested Citation

  • Zhongbin Deng & Jingyao Mu & Michael Tseng & Binks Wattenberg & Xiaoying Zhuang & Nejat K. Egilmez & Qilong Wang & Lifeng Zhang & James Norris & Haixun Guo & Jun Yan & Bodduluri Haribabu & Donald Mill, 2015. "Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7956
    DOI: 10.1038/ncomms7956
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