Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation

Naoteru Miyata, Lindsey L. Morris, Qing Chen, Curtis Thorne, Amika Singla, Wenhan Zhu, Maria Winter, Shelby D. Melton, Haiying Li, Luis Sifuentes-Dominguez, Ernesto Llano, Kayci Huff-Hardy, Petro Starokadomskyy, Adam Lopez, Tiffany A. Reese, Emre Turer, Daniel D. Billadeau, Sebastian E. Winter, Ezra Burstein

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Physiologic microbe-host interactions in the intestine require the maintenance of the microbiota in a luminal compartment through a complex interplay between epithelial and immune cells. However, the roles of mucosal myeloid cells in this process remain incompletely understood. In this study, we identified that decreased myeloid cell phagocytic activity promotes colon tumorigenesis. We show that this is due to bacterial accumulation in the lamina propria and present evidence that the underlying mechanism is bacterial induction of prostaglandin production by myeloid cells. Moreover, we show that similar events in the normal colonic mucosa lead to reductions in Tuft cells, goblet cells, and the mucus barrier of the colonic epithelium. These alterations are again linked to the induction of prostaglandin production in response to bacterial penetration of the mucosa. Altogether, our work highlights immune cell-epithelial cell interactions triggered by the microbiota that control intestinal immunity, epithelial differentiation, and carcinogenesis. Miyata et al. find that defective bacterial elimination by intestinal myeloid cells promotes prostaglandin production and drives excess colonic neoplasia in a genetic mouse model. Moreover, in the normal mucosa, similar prostaglandin overproduction suppresses differentiation of mucus-producing goblet cells through direct effects on Tuft cells, a regulator of goblet cells.

Original languageEnglish (US)
Pages (from-to)2342-2355
Number of pages14
JournalCell Reports
Volume24
Issue number9
DOIs
StatePublished - Aug 28 2018

Keywords

  • CCC complex
  • COX-2
  • Commd1
  • PGE-2
  • Tuft cells
  • colon cancer
  • goblet cells
  • intestinal microbiota
  • myeloid cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Miyata, N., Morris, L. L., Chen, Q., Thorne, C., Singla, A., Zhu, W., Winter, M., Melton, S. D., Li, H., Sifuentes-Dominguez, L., Llano, E., Huff-Hardy, K., Starokadomskyy, P., Lopez, A., Reese, T. A., Turer, E., Billadeau, D. D., Winter, S. E., & Burstein, E. (2018). Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation. Cell Reports, 24(9), 2342-2355. https://doi.org/10.1016/j.celrep.2018.07.066