The Cytosolic Bacterial Peptidoglycan Sensor Nod2 Affords Stem Cell Protection and Links Microbes to Gut Epithelial Regeneration
The Cytosolic Bacterial Peptidoglycan Sensor Nod2 Affords Stem Cell Protection and Links Microbes to Gut Epithelial Regeneration
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DOI：
10.1016/j.chom.2014.05.003
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发表时间：
2014-06-11
影响因子：
30.3
通讯作者：
Sansonetti, Philippe J.
中科院分区：
文献类型：
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作者：
Nigro, Giulia;Rossi, Raffaella;Sansonetti, Philippe J.
肠隐窝是微生物群产物、干细胞和在该生态位中发现的其他细胞类型（包括潘氏细胞）之间的潜在相互作用的部位，因此为肠道微生物影响宿主上皮提供了可能性。然而，这种微环境的复杂性一直是破译潜在机制的挑战。我们使用体外培养的小鼠肠隐窝类器官，用体内实验加强，以检查隐窝-微生物群界面。我们发现，在肠隐窝内，Lgr 5（+）干细胞组成型表达胞质先天免疫传感器Nod 2的水平远高于潘氏细胞。Nod 2通过其真正的激动剂胞壁酰二肽（MDP）（所有细菌共有的肽聚糖基序）刺激，触发干细胞存活，从而导致对氧化应激介导的细胞死亡的强烈细胞保护。因此，肠道上皮恢复是Nod 2依赖性的，并由微生物群衍生分子的存在触发。
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.