Luminal Microbes Promote Monocyte–Stem Cell Interactions Across a Healthy Colonic Epithelium
| Autor: | Nikki Horn, Petr Walczysko, Anastasia Sobolewski, Dagmara A. Skoczek, Mark Williams, Simon Clare, Alyson Parris |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Immunology Mice Transgenic Biology Monocytes Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Intestinal mucosa medicine Animals Antigens Ly Humans Immunology and Allergy Intestinal Mucosa Tissue homeostasis Cell Proliferation 030304 developmental biology 0303 health sciences Bacteria Cell growth Stem Cells Monocyte Mucosal Immunology Intestinal epithelium Epithelium Gut Epithelium Cell biology medicine.anatomical_structure Female Stem cell 030215 immunology |
| Zdroj: | The Journal of Immunology Author Choice |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1301497 |
| Popis: | The intestinal epithelium forms a vital barrier between luminal microbes and the underlying mucosal immune system. Epithelial barrier function is maintained by continuous renewal of the epithelium and is pivotal for gut homeostasis. Breaching of the barrier causes mobilization of immune cells to promote epithelial restitution. However, it is not known whether microbes at the luminal surface of a healthy epithelial barrier influence immune cell mobilization to modulate tissue homeostasis. Using a mouse colonic mucosal explant model, we demonstrate that close proximity of luminal microbes to a healthy, intact epithelium results in rapid mucus secretion and movement of Ly6C+7/4+ monocytes closer to epithelial stem cells. These early events are driven by the epithelial MyD88-signaling pathway and result in increased crypt cell proliferation and intestinal stem cell number. Over time, stem cell number and monocyte–crypt stem cell juxtapositioning return to homeostatic levels observed in vivo. We also demonstrate that reduced numbers of tissue Ly6C+ monocytes can suppress Lgr5EGFP+ stem cell expression in vivo and abrogate the response to luminal microbes ex vivo. The functional link between monocyte recruitment and increased crypt cell proliferation was further confirmed using a crypt–monocyte coculture model. This work demonstrates that the healthy gut epithelium mediates communication between luminal bacteria and monocytes, and monocytes can modulate crypt stem cell number and promote crypt cell proliferation to help maintain gut homeostasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|