Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation
| Autor: | Qing Chen, Tiffany A. Reese, Amika Singla, Luis Sifuentes-Dominguez, Shelby D. Melton, Kayci Huff-Hardy, Emre E. Turer, Naoteru Miyata, Ernesto M. Llano, Wenhan Zhu, Haiying Li, Sebastian E. Winter, Curtis A. Thorne, Petro Starokadomskyy, Lindsey L. Morris, Adam M. Lopez, Daniel D. Billadeau, Ezra Burstein, Maria G. Winter |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
intestinal microbiota Myeloid goblet cells Colorectal cancer Carcinogenesis Cell Medical Physiology Tuft cells Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Oral and gastrointestinal Article 03 medical and health sciences Mice 0302 clinical medicine Immune system medicine Compartment (development) 2.1 Biological and endogenous factors Animals Humans Myeloid Cells Aetiology PGE-2 Cancer Lamina propria Inflammatory and immune system Microbiota Epithelial Cells COX-2 medicine.disease Mucus 3. Good health Cell biology Colo-Rectal Cancer Intestines 030104 developmental biology medicine.anatomical_structure colon cancer 030220 oncology & carcinogenesis CCC complex Commd1 Biochemistry and Cell Biology Digestive Diseases |
| Zdroj: | Cell reports Cell reports, vol 24, iss 9 |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. In Brief 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. Graphical Abstract |
| Databáze: | OpenAIRE |
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