Study of immunomodulation on the intestinal immune responses by saccharides

双歧杆菌免疫调节剂（BIM）由水溶性多糖和肽聚糖组成，预期可调节宿主的免疫应答。我们证明了连续7天口服细菌多糖BIM诱导小鼠淋巴组织（派伊尔集合淋巴结; PP，肠系膜淋巴结; MLN和脾脏; SPL）的免疫应答（例如细胞因子产生）。本研究旨在阐明口服单次注射BIM后BIM在宿主肠道相关淋巴组织中的分布，并研究口服给药后作为粘膜伊加分泌效应位点的固有层（LP）的免疫应答。观察BIM在PP和LP中的分布。我们已经证明，BIM在口服给药后1小时到达PP和小肠LP（S-LP），并且在PP组织切片中观察到的DIM分布位置与CD 11 c ^+细胞几乎相同。然后，BIM在口服给药后18小时到达MLN。这些结果表明，在PP中BIM可能直接穿过绒毛M细胞，并可能被CD 11 c ^+细胞如树突状细胞等内吞和加工。结果表明，BIM可能通过肠上皮细胞的紧密连接直接进入LP，而不通过共同粘膜免疫系统（CMIS）进入LP，并在单次给药后1h内被DC等CD 11 ^+细胞吞噬。LPL细胞因子和伊加反应的研究结果表明，BIM可能通过BIM喂养刺激S-LPL分泌伊加和细胞因子。此外，BIM在小肠和大肠之间的肠段可诱导不同的LPL免疫反应。

Bifidobacterium immunomodulators (BIM) are composed of water-soluble polysaccharides and peptidoglycans, which are expected to modulate immune responses in the host. We demonstrated that oral administration of bacterial polysaccharides, BIM for 7 consecutive days induced the immunoresponses (e.g. cytokine production) on the murine lymphoid tissues (Peyer's patch ; PP, mesenteric lymphoid nodes ; MLN, and spleen ; SPL). This study is to clarify the distribution of BIM in the host gut-associated lymphoid tissues after single-shot administration of BIM orally, and we are investigating the immune responses of lamina propropria (LP) as an effector site for mucosal IgA secretion by oral administration. We observed the distribution of BIM in PP and LP after oral administration. We have shown that the BIM reached PP and small intestinal LP (S-LP) at the passed time of 1 hour after oral administration and the location of DIM distribution observed in PP tissue sections were almost as same as CD11c^+ cells. Then, BIM reached MLN at the passed time of 18 hours after oral administration. These results suggested that the BIM might pass through the villous M-cells directly and might be endcytosed and processed by CD11c^+ cell such as dendritic cells in PP. It was also suggested that the BIM might pass through the tight junctions of intestinal epithelial cells into LP directly, but not through the common mucosal immune system (CMIS), and then the BIM might be endcytosed by CD11^+ cell such as dendritic cell orally at the passed time of 1 hour after single-shot administration. The findings of the cytokines and IgA responses of LPL indicated that BIM might stimulate S-LPL to secrete IgA and cytokines by BIM feeding. In addition, It suggested that BIM could induce different immunoreactions of LPL in the intestinal location between small intestine and large intestine.