期刊
CELL HOST & MICROBE
卷 15, 期 6, 页码 792-798出版社
CELL PRESS
DOI: 10.1016/j.chom.2014.05.003
关键词
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资金
- European Research Council (ERC)
- ERC
- DIM-STEM-Pole Ile-de-France cellules souches et medecine''
The intestinal crypt is a site of potential interactions between microbiota products, stem cells, and other cell types found in this niche, including Paneth cells, and thus offers a potential for commensal microbes to influence the host epithelium. However, the complexity of this microenvironment has been a challenge to deciphering the underlying mechanisms. We used in vitro cultured organoids of intestinal crypts from mice, reinforced with in vivo experiments, to examine the crypt-microbiota interface. We find that within the intestinal crypt, Lgr5(+) stem cells constitutively express the cytosolic innate immune sensor Nod2 at levels much higher than in Paneth cells. Nod2 stimulation by its bona fide agonist, muramyldipeptide (MDP), a peptidoglycan motif common to all bacteria, triggers stem cell survival, which leads to a strong cytoprotection against oxidative stress-mediated cell death. Thus, gut epithelial restitution is Nod2 dependent and triggered by the presence of microbiota-derived molecules.
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