Work

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

Year: 2015

Type: article

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. Microbial and host cells in the gut exchange complex signals that we only begin to decipher. Here the authors show that pathogenic but not commensal gut bacteria secrete microparticles, which in turn induce changes in the content of the mucosa-produced exosomes to promote Th17-mediated tumorigenesis.

Source: Nature Communications

DOI: 10.1038/ncomms7956