Commensal Gram-positive bacteria initiates colitis by inducing monocyte/macrophage mobilization
Commensal Gram-positive bacteria initiates colitis by inducing monocyte/macrophage mobilization
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DOI：
10.1038/mi.2014.53
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发表时间：
2015-01-01
影响因子：
8
通讯作者：
Ohteki, T.
中科院分区：
文献类型：
--
作者：
Nakanishi, Y.;Sato, T.;Ohteki, T.
肠上皮层屏障功能的破坏导致肠道植物群的流入和针对肠道植物群的不适当的免疫应答，导致炎症性肠病（IBD）的发展。使用小鼠葡聚糖硫酸钠（DSS）诱导的结肠炎模型，我们在这里显示，大肠杆菌革兰氏阳性细菌触发炎症单核细胞和巨噬细胞进入结肠的动员。单核细胞/巨噬细胞是肿瘤坏死因子-α（TNF-α）的主要生产者，肿瘤坏死因子-α是使结肠炎恶化的代表性细胞因子。值得注意的是，用万古霉素预处理小鼠，其消除革兰氏阳性细菌，特别是毛螺菌科，通过选择性地阻断单核细胞/巨噬细胞的募集而不是其他细胞的募集，显著降低了结肠炎的严重程度。重要的是，万古霉素治疗特异性下调C-C趋化因子受体2型（CCR 2）配体的结肠上皮细胞（cEC）表达，C-C趋化因子受体2型（CCR 2）配体是单核细胞/巨噬细胞动员进入发炎结肠的关键趋化因子。总的来说，这些结果提供了以前未发现的证据，即革兰氏阳性大肠杆菌通过募集致结肠炎单核细胞和巨噬细胞诱导结肠炎。我们的研究结果可能会导致IBD治疗的新途径。
Breakdown of the intestinal epithelial layer's barrier function results in the inflow of commensal flora and improper immune responses against the commensal flora, leading to inflammatory bowel disease (IBD) development. Using a mouse dextran sodium sulfate (DSS)-induced colitis model, we show here that commensal Gram-positive bacteria trigger the mobilization of inflammatory monocytes and macrophages into the colon. Monocytes/macrophages are major producers of tumor necrosis factor-alpha (TNF-alpha), a representative cytokine that aggravates colitis. Notably, pretreating mice with vancomycin, which eliminated Gram-positive bacteria, particularly the Lachnospiraceae family, significantly reduced the severity of the colitis by selectively blocking the recruitment of monocytes/macrophages, but not of other cells. Importantly, vancomycin treatment specifically downregulated the colonic epithelial cell (cEC) expression of C-C chemokine receptor type-2 (CCR2) ligands, which are critical chemokines for monocyte/macrophage mobilization into the inflamed colon. Collectively, these results provide previously undiscovered evidence that Gram-positive commensal bacteria induce colitis by recruiting colitogenic monocytes and macrophages. Our findings may lead to new avenues of treatment for IBD.