Sellon R K, Tonkonogy S, Schultz M, Dieleman L A, Grenther W, Balish E, Rennick D M, Sartor R B
Department of Companion Animal and Special Species, Pathology and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
Infect Immun. 1998 Nov;66(11):5224-31. doi: 10.1128/IAI.66.11.5224-5231.1998.
Mice with targeted deletion of the gene for interleukin-10 (IL-10) spontaneously develop enterocolitis when maintained in conventional conditions but develop only colitis when kept in specific-pathogen-free (SPF) environments. This study tested the hypothesis that enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice. IL-10-deficient mice were maintained in either SPF conditions or germfree conditions or were populated with bacteria known to cause colitis in other rodent models. IL-10-deficient mice kept in SPF conditions developed colitis in all segments of the colon (cecum and proximal and distal colon). These mice exhibited immune system activation as evidenced by increased expression of CD44 on CD4(+) T cells; increased mesenteric lymph node cell numbers; and increased production of immunoglobulin A (IgA), IgG1, and IL-12 p40 from colon fragment cultures. Mice populated with bacterial strains, including Bacteroides vulgatus, known to induce colitis in other rodent models had minimal colitis. Germfree IL-10-deficient mice had no evidence of colitis or immune system activation. We conclude therefore that resident enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice.
白细胞介素-10（IL-10）基因靶向缺失的小鼠在常规条件下饲养时会自发发生小肠结肠炎，但在无特定病原体（SPF）环境中饲养时仅发生结肠炎。本研究检验了以下假说：肠道细菌对于IL-10缺陷小鼠自发性结肠炎的发生及免疫系统激活是必需的。将IL-10缺陷小鼠饲养于SPF条件或无菌条件下，或接种在其他啮齿动物模型中已知会引起结肠炎的细菌。饲养于SPF条件下的IL-10缺陷小鼠在结肠的所有节段（盲肠以及近端和远端结肠）均发生了结肠炎。这些小鼠表现出免疫系统激活，表现为CD4(+) T细胞上CD44表达增加；肠系膜淋巴结细胞数量增加；以及结肠片段培养物中免疫球蛋白A（IgA）、IgG1和IL-12 p40的产生增加。接种包括在其他啮齿动物模型中已知会诱导结肠炎的普通拟杆菌等细菌菌株的小鼠结肠炎很轻微。无菌的IL-10缺陷小鼠没有结肠炎或免疫系统激活的迹象。因此，我们得出结论，常驻肠道细菌对于IL-10缺陷小鼠自发性结肠炎的发生及免疫系统激活是必需的。
