Dataset Information

Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation.

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.

SUBMITTER: Miyata N

PROVIDER: S-EPMC6177233 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation.

Miyata Naoteru N Morris Lindsey L LL Chen Qing Q Thorne Curtis C Singla Amika A Zhu Wenhan W Winter Maria M Melton Shelby D SD Li Haiying H Sifuentes-Dominguez Luis L Llano Ernesto E Huff-Hardy Kayci K Starokadomskyy Petro P Lopez Adam A Reese Tiffany A TA Turer Emre E Billadeau Daniel D DD Winter Sebastian E SE Burstein Ezra E

Cell reports 20180801 9

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 ...[more]

PMID: 30157428

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Project description:Background & aimsThe intestinal epithelium functions both in nutrient absorption and as a barrier, separating the luminal contents from a network of vascular, fibroblastic, and immune cells underneath. After injury to the intestine, multiple cell populations cooperate to drive regeneration of the mucosal barrier, including lymphatic endothelial cells (LECs). A population of granulocytic immature myeloid cells (IMCs), marked by Hdc, participate in regeneration of multiple organs such as the colon and central nervous system, and their contribution to intestinal regeneration was investigated.MethodsBy using male and female histidine decarboxylase (Hdc) green fluorescent reporter (GFP) mice, we investigated the role of Hdc+ IMCs in intestinal regeneration after exposure to 12 Gy whole-body irradiation. The movement of IMCs was analyzed using flow cytometry and immunostaining. Ablation of Hdc+ cells using the HdcCreERT2 tamoxifen-inducible recombinase Cre system, conditional knockout of Prostaglandin-endoperoxidase synthase 2 (Ptgs2) in Hdc+ cells using HdcCre; Ptgs2 floxed mice, and visualization of LECs using Prox1tdTomato mice also was performed. The role of microbial signals was investigated by knocking down mice gut microbiomes using antibiotic cocktail gavages.ResultsWe found that Hdc+ IMCs infiltrate the injured intestine after irradiation injury and promote epithelial regeneration in part by modulating LEC activity. Hdc+ IMCs express Ptgs2 (encoding cyclooxygenase-2/COX-2), and enables them to produce prostaglandin E2. Prostaglandin E2 acts on the prostaglandin E2 receptor 4 receptor (EP4) on LECs to promote lymphangiogenesis and induce the expression of proregenerative factors including R-spondin 3. Depletion of gut microbes leads to reduced intestinal regeneration by impaired recruitment of IMCs.ConclusionsAltogether, our results unveil a critical role for IMCs in intestinal repair by modulating LEC activity and implicate gut microbes as mediators of intestinal regeneration.

Dataset Information

Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation.

Publications

Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation.

Similar Datasets

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