Transitions in Oral and Intestinal Microflora Composition and Innate Immune Receptor-Dependent Stimulation during Mouse Development
Transitions in Oral and Intestinal Microflora Composition and Innate Immune Receptor-Dependent Stimulation during Mouse Development
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DOI：
10.1128/iai.01043-09
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发表时间：
2010-02-01
影响因子：
3.1
通讯作者：
Inohara, Naohiro
中科院分区：
文献类型：
--
作者：
Hasegawa, Mizuho;Osaka, Toshifumi;Inohara, Naohiro
共生细菌具有免疫刺激活性，可以调节宿主反应以影响肠道的发育和稳态。然而，不同的常驻细菌群体如何刺激免疫系统仍然是未知的。我们的特点是在这里的能力，肠道和口腔微生物菌群刺激骨髓来源的巨噬细胞和间皮细胞的个人模式识别受体（PRRs）。肠道而不是口腔微生物群落引起了年龄和细胞类型特异性的免疫刺激。肠道菌群的免疫刺激活性在个体小鼠中各不相同，但在母乳喂养期间主要通过Toll样受体4（TLR 4）介导，而在断奶后变得不依赖TLR 4。这种转变与从富含TLR 4刺激蛋白菌的微生物区系到以类杆菌目和/或梭菌目为主的微生物区系的变化有关，而类杆菌目和/或梭菌目很少刺激TLR 4。肠道微生物群落的主要刺激活性在NOD 1-、NOD 2-、TLR 2-、TLR 4-、TLR 5-、TLR 9-、TLR 11-、ASC-或RICK-缺陷细胞中仍然是完整的，但仍然依赖于衔接子MyD 88。这些研究表明，肠道菌群的转变伴随着其刺激控制肠道稳态的不同PRR的能力的动态变化。
Commensal bacteria possess immunostimulatory activities that can modulate host responses to affect development and homeostasis in the intestine. However, how different populations of resident bacteria stimulate the immune system remains largely unknown. We characterized here the ability of intestinal and oral microflora to stimulate individual pattern recognition receptors (PRRs) in bone marrow-derived macrophages and mesothelial cells. The intestinal but not oral microflora elicited age-and cell type-specific immunostimulation. The immunostimulatory activity of the intestinal microflora varied among individual mice but was largely mediated via Toll-like receptor 4 (TLR4) during breast-feeding, whereas it became TLR4 independent after weaning. This transition was associated with a change from a microflora rich in TLR4-stimulatory proteobacteria to one dominated by Bacteroidales and/or Clostridiales that poorly stimulate TLR4. The major stimulatory activity of the intestinal microflora was still intact in NOD1-, NOD2-, TLR2-, TLR4-, TLR5-, TLR9-, TLR11-, ASC-, or RICK-deficient cells but still relied on the adaptor MyD88. These studies demonstrate a transition in the intestinal microflora accompanied by a dynamic change of its ability to stimulate different PRRs which control intestinal homeostasis.