Toll-like receptor 2 and 9 are expressed and functional in gut-associated lymphoid tissues of presuckling newborn swine
Toll-like receptor 2 and 9 are expressed and functional in gut-associated lymphoid tissues of presuckling newborn swine
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DOI：
10.1051/vetres:2006036
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发表时间：
2006-11-01
影响因子：
4.4
通讯作者：
Kitazawa, Haruki
中科院分区：
文献类型：
--
作者：
Tohno, Masanori;Shimosato, Takeshi;Kitazawa, Haruki
an8 为了阐明 Toll 样受体 (TLR) 2 和 TLR9 在未成熟肠道相关淋巴组织 (GALT) 中的关键作用，我们重点研究了 TLR2 和 TLR9 的表达及其配体在哺乳前新生猪 GALT 中诱导的免疫反应。定量实时 PCR 显示，TLR2 和 TLR9 mRNA 在所有测试组织（心脏、胸腺、肺、脾、肝、肾、骨骼肌、十二指肠、空肠、回肠、回肠集合淋巴结 (Pps) 和肠系膜淋巴结 (MLN)）中均以可检测水平表达。特别是，在未成熟肠组织和 GALT 中，TLR2 和 TLR9 mRNA 在回肠 Pps 和 MLN 中的表达水平高于十二指肠、空肠和回肠。我们证实 TLR2 和 TLR9 蛋白也高度表达，并且它们的配体优先被 MLN 和回肠 Pps 中表达 TLR2 或 TLR9 的细胞识别。酵母聚糖、CpG2006 和乳酸菌可以促进 MLN 和回肠 Pps 的有丝分裂和多种细胞因子的产生。此外，细胞角蛋白 18 和 TLR2 或 TLR9 的双重免疫染色显示，TLR2 和 TLR9 在柱状膜 (M) 细胞中强烈表达。有趣的是，虽然柱状M细胞的顶膜强烈表达TLR2蛋白并优先识别酵母聚糖，但“顶膜上的TLR2表达”和“TLR2介导的酵母聚糖结合”在邻近的肠细胞中都可以忽略不计。这些结果表明，TLR2和TLR9允许MLN和回肠Pps在出生后立即对多种细菌成分做出反应，从而为新生儿提供宿主防御系统。
an8 To clarify the crucial role of Toll-like receptor (TLR) 2 and TLR9 in immature gut-associated lymphoid tissues (GALT), we focused on the expression of TLR2 and TLR9 and the immune responses induced by their ligands in the GALT of presuckling newborn swine. Quantitative real-time PCR revealed that TLR2 and TLR9 mRNA were expressed at detectable levels in all tested tissues ( heart, thymus, lung, spleen, liver, kidney, skeletal muscle, duodenum, jejunum, ileum, ileal Peyer patches (Pps), and mesenteric lymph nodes (MLN)). In particular, in immature intestinal tissues and GALT, TLR2 and TLR9 mRNA were expressed at higher levels in ileal Pps and MLN than in the duodenum, jejunum, and ileum. We confirmed that the TLR2 and TLR9 proteins were also highly expressed and that their ligands were preferentially recognized by TLR2- or TLR9-expressing cells in the MLN and ileal Pps. Zymosan, CpG2006, and lactic acid bacteria could promote mitogenesis and production of multiple cytokines by the MLN and ileal Pps. In addition, double immunostaining for cytokeratin 18 and either TLR2 or TLR9 revealed that both TLR2 and TLR9 are strongly expressed in the columnar membranous ( M) cells. Interestingly, while the apical membrane of the columnar M cells strongly expressed TLR2 protein and preferentially recognized zymosan, both "TLR2 expression on the apical membrane" and "TLR2-mediated zymosan binding" were negligible in neighboring enterocytes. These results indicate that TLR2 and TLR9 allow MLN and ileal Pps to respond to a variety of bacterial components immediately after birth, thereby providing newborns with a host defense system.