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首页> 外文期刊>Infection and immunity >Helicobacter hepaticus Triggers Colitis in Specific-Pathogen-Free Interleukin-10 (IL-10)-Deficient Mice through an IL-12- and Gamma Interferon-Dependent Mechanism
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Helicobacter hepaticus Triggers Colitis in Specific-Pathogen-Free Interleukin-10 (IL-10)-Deficient Mice through an IL-12- and Gamma Interferon-Dependent Mechanism

机译：肝杆菌通过IL-12和γ干扰素依赖性机制在无特定病原性白介素10（IL-10）缺陷的小鼠中引发结肠炎。

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Mice rendered deficient in interleukin-10 (IL-10) by gene targeting (IL-10?/? mice) develop chronic enterocolitis resembling human inflammatory bowel disease (IBD) when maintained in conventional animal facilities. However, they display a minimal and delayed intestinal inflammatory response when reared under specific-pathogen-free (SPF) conditions, suggesting the involvement of a microbial component in pathogenesis. We show here that experimental infection with a single bacterial agent, Helicobacter hepaticus, induces chronic colitis in SPF-reared IL-10?/? mice and that the disease is accompanied by a type 1 cytokine response (gamma interferon [IFN-γ], tumor necrosis factor alpha, and nitric oxide) detected by restimulation of spleen and mesenteric lymph node cells with a soluble H. hepaticusantigen (Ag) preparation. In contrast, wild-type (WT) animals infected with the same bacteria did not develop disease and produced IL-10 as the dominant cytokine in response to Helicobacter Ag. Strong H. hepaticus-reactive antibody responses as measured by Ag-specific total immunoglobulin G (IgG), IgG1, IgG2a, IgG2b, IgG3, and IgA were observed in both WT and IL-10?/? mice. In vivo neutralization of IFN-γ or IL-12 resulted in a significant reduction of intestinal inflammation in H. hepaticus-infected IL-10?/? mice, suggesting an important role for these cytokines in the development of colitis in the model. Taken together, these microbial reconstitution experiments formally establish that a defined bacterial agent can serve as the immunological target in the development of large bowel inflammation in IL-10?/? mice and argue that in nonimmunocompromised hosts IL-10 stimulated in response to intestinal flora is important in preventing IBD.
机译：通过基因靶向（IL-10 ？/？小鼠）使白介素10（IL-10）缺乏的小鼠在常规动物设施中饲养时会发展为类似于人类炎性肠病（IBD）的慢性小肠结肠炎。但是，当在无特定病原体（SPF）的条件下饲养时，它们显示出最小的和延迟的肠道炎症反应，表明微生物成分参与了发病机理。我们在这里表明，用单一细菌菌 Helicobacter hepaticus 进行的实验感染在SPF饲养的IL-10 ？/？小鼠中诱发慢性结肠炎，并且该疾病伴随通过用可溶性H重新刺激脾脏和肠系膜淋巴结细胞而检测到的1型细胞因子反应（γ干扰素[IFN-γ]，肿瘤坏死因子α和一氧化氮）。肝抗原（Ag）的制备。相比之下，感染相同细菌的野生型（WT）动物没有发生疾病，并且对 Helicobacter Ag产生了IL-10作为优势细胞因子。强 H。用Ag特异性总免疫球蛋白G（IgG），IgG1，IgG2a，IgG2b，IgG3和IgA检测到的肝反应抗体应答在WT和IL-10 ？/？老鼠。体内中和IFN-γ或IL-12可显着降低 H肠道炎症。感染了肝的IL-10 ？/？小鼠，表明这些细胞因子在该模型的结肠炎发展中具有重要作用。综上所述，这些微生物重建实验正式建立了一种确定的细菌剂可以作为IL-10 ？/？小鼠大肠炎症发展的免疫学靶标，并指出在非免疫受损的宿主中IL-响应肠道菌群刺激而产生的10对预防IBD很重要。

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