Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium
Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium
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DOI：
10.1016/s0002-9440(10)64360-x
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发表时间：
2002-01-01
影响因子：
6
通讯作者：
Podolsky, DK
中科院分区：
文献类型：
--
作者：
Cario, E;Brown, D;Podolsky, DK
共生相关分子模式是非病原性细菌的主要产物，以高浓度存在于肠上皮的顶端表面。然而，共生相关分子模式与上皮腔表面相互作用的性质尚未确定。我们最近证明，肠上皮细胞在体外和体内持续表达多种 Toll 样受体 (TLR)，这些受体似乎是负责响应各种细菌产物而激活免疫细胞的关键受体。在本研究中，我们描述了两种主要 TLR（TLR2 和 TLR4）的亚细胞分布，以及它们在模型人肠上皮细胞 Fine T84 中的配体特异性动态调节。免疫细胞化学研究表明，TLR2 和 TLR4 在分化的 T84 细胞的顶极持续表达。在用脂多糖或肽聚糖刺激后，TLR 选择性地运输到基底外侧膜附近的细胞质区室。因此，我们证明 TLR 位于顶极，在那里它们可以监测腔内微生物阵列的敏感平衡。然后，这种动态上皮监视的结果可以通过这些先天免疫模式识别受体传递到固有层的底层细胞群。
Commensal-associated molecular patterns, the major products of nonpathogenic bacteria, are present at high concentrations at the apical surface of the intestinal epithelium. However, the nature of the interaction of commensal-associated molecular patterns with the lumenal surface of the epithelium has not been defined. We have recently demonstrated that intestinal epithelial cells constitutively express several Toll-like receptors (TLRs) in vitro and in vivo that seem to be the key receptors responsible for immune cell activation in response to various bacterial products. In this study we characterize the subcellular distribution of two major TLRs, TLR2 and TLR4, and their ligand-specific dynamic regulation in the model human intestinal epithelial cell fine T84. Immunocytochemical studies indicate that TLR2 and TLR4 are constitutively expressed at the apical pole of differentiated T84 cells. After stimulation with lipopolysaccharide or peptidoglycan, TLRs selectively traffic to cytoplasmic compartments near the basolateral membrane. Thus, we demonstrate that TLRs are positioned at the apical pole where they are poised to monitor the sensitive balance of the lumenal microbial array. The results of this dynamic epithelial surveillance can then be conveyed to the underlying cell populations of the lamina propria via these innate immune pattern recognition receptors.