Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Cell Host Microbe. 2013 Jun 12;13(6):711-22. doi: 10.1016/j.chom.2013.05.013.
Imbalance in gut bacterial composition provokes host proinflammatory responses causing diseases such as colitis. Colonization with a mixture of Clostridium species from clusters IV and XIVa was shown to suppress colitis through the induction of IL-10-producing regulatory T (Treg) cells. We demonstrate that a distinct Clostridium strain from cluster I, Clostridium butyricum (CB), prevents acute experimental colitis in mice through induction of IL-10, an anti-inflammatory cytokine. However, while CB treatment had no effect on IL-10 production by T cells, IL-10-producing F4/80(+)CD11b(+)CD11c(int) macrophages accumulated in the inflamed mucosa after CB treatment. CB directly triggered IL-10 production by intestinal macrophages in inflamed mucosa via the TLR2/MyD88 pathway. The colitis-preventing effect of CB was negated in macrophage-specific IL-10-deficient mice, suggesting that induction of IL-10 by intestinal macrophages is crucial for the probiotic action of CB. Collectively, CB promotes IL-10 production by intestinal macrophages in inflamed mucosa, thereby preventing experimental colitis in mice.
肠道细菌组成失衡会引发宿主炎症反应，导致结肠炎等疾病。研究表明，来自 IV 簇和 XIVa 簇的混合 Clostridium 物种定植可通过诱导产生 IL-10 的调节性 T（Treg）细胞来抑制结肠炎。我们证明，来自 I 簇的一种独特的梭状芽孢杆菌，丁酸梭菌（CB），通过诱导抗炎细胞因子 IL-10 来预防小鼠的急性实验性结肠炎。然而，虽然 CB 处理对 T 细胞产生 IL-10 没有影响，但在 CB 处理后，IL-10 产生的 F4/80(+)CD11b(+)CD11c(int)巨噬细胞在发炎的黏膜中积累。CB 通过 TLR2/MyD88 途径直接触发炎症黏膜中肠道巨噬细胞产生 IL-10。在巨噬细胞特异性 IL-10 缺陷型小鼠中，CB 预防结肠炎的作用被否定，这表明肠道巨噬细胞诱导产生 IL-10 对于 CB 的益生菌作用至关重要。总之，CB 促进炎症黏膜中肠道巨噬细胞产生 IL-10，从而预防小鼠的实验性结肠炎。
