Krause Petra, Morris Venetia, Greenbaum Jason A, Park Yoon, Bjoerheden Unni, Mikulski Zbigniew, Muffley Tracy, Shui Jr-Wen, Kim Gisen, Cheroutre Hilde, Liu Yun-Cai, Peters Bjoern, Kronenberg Mitchell, Murai Masako
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
Bioinformatics Core Facility, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
Nat Commun. 2015 May 11;6:7055. doi: 10.1038/ncomms8055.
Innate immune responses are regulated in the intestine to prevent excessive inflammation. Here we show that a subset of mouse colonic macrophages constitutively produce the anti-inflammatory cytokine IL-10. In mice infected with Citrobacter rodentium, a model for enteropathogenic Escherichia coli infection in humans, these macrophages are required to prevent intestinal pathology. IL-23 is significantly increased in infected mice with a myeloid cell-specific deletion of IL-10, and the addition of IL-10 reduces IL-23 production by intestinal macrophages. Furthermore, blockade of IL-23 leads to reduced mortality in the context of macrophage IL-10 deficiency. Transcriptome and other analyses indicate that IL-10-expressing macrophages receive an autocrine IL-10 signal. Interestingly, only transfer of the IL-10 positive macrophages could rescue IL-10-deficient infected mice. Therefore, these data indicate a pivotal role for intestinal macrophages that constitutively produce IL-10, in controlling excessive innate immune activation and preventing tissue damage after an acute bacterial infection.
肠道中的固有免疫反应受到调节以防止过度炎症。我们在此表明，小鼠结肠巨噬细胞的一个亚群组成性地产生抗炎细胞因子白细胞介素-10（IL-10）。在感染啮齿柠檬酸杆菌（一种人类肠道致病性大肠杆菌感染的模型）的小鼠中，这些巨噬细胞对于预防肠道病变是必需的。在髓系细胞特异性缺失IL-10的感染小鼠中，白细胞介素-23（IL-23）显著增加，并且添加IL-10可减少肠道巨噬细胞产生IL-23。此外，在巨噬细胞IL-10缺乏的情况下，阻断IL-23可降低死亡率。转录组和其他分析表明，表达IL-10的巨噬细胞接收自分泌的IL-10信号。有趣的是，仅转移IL-10阳性巨噬细胞就能挽救IL-10缺陷的感染小鼠。因此，这些数据表明组成性产生IL-10的肠道巨噬细胞在控制急性细菌感染后过度的固有免疫激活和防止组织损伤方面起着关键作用。
