Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice
Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice
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DOI：
10.1128/iai.67.5.2585-2589.1999
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发表时间：
1999-05-01
影响因子：
3.1
通讯作者：
Akira, S
中科院分区：
文献类型：
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作者：
Sugawara, I;Yamada, H;Akira, S
对分枝杆菌感染的免疫与T细胞的出现密切相关，T细胞分泌细胞因子、γ干扰素（ifn - γ）、白细胞介素-12 （IL-12）和肿瘤坏死因子α (tnf - α)，导致巨噬细胞活化和循环单核细胞募集，引发慢性肉芽肿形成。介导巨噬细胞活化的细胞因子是ifn - γ，与IL-12一样，IL-18被证明可以激活Th1细胞并诱导这些细胞产生ifn - γ。为了研究IL-18在分枝杆菌感染中的作用，我们用结核分枝杆菌和牛分枝杆菌感染了IL-18缺失的小鼠，研究了它们控制细菌生长、肉芽肿形成、细胞因子分泌和NO产生的能力。这些小鼠的肺和脾脏出现了明显的肉芽肿，但没有坏死。与野生型小鼠相比，il -18缺失小鼠脾脏ifn - γ水平较低，IL-12水平正常。ifn - γ产生的减少不是继发于诱导IL-12产生的减少。il -18缺失小鼠和野生型小鼠腹腔巨噬细胞产生NO的水平无显著差异。外源性重组IL-18可显著抑制IL-18缺失小鼠肉芽肿病变的发展，因此IL-18对分枝杆菌保护性免疫的产生具有重要作用，其主要功能是诱导ifn - γ的表达。
Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-gamma), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha), resulting in macrophage activation and recruitment of circulating monocytes to initiate chronic granuloma formation. The cytokine that mediates macrophage activation is IFN-gamma, and, like IL-12, IL-18 was shown to activate Th1 cells and induce IFN-gamma production by these cells, In order to investigate the role of IL-18 in mycobacterial infection, IL-18-deficient mice were infected with Mycobacterium tuberculosis and Mycobacterium bovis BCG Pasteur, and their capacities to control bacterial growth, granuloma formation, cytokine secretion, and NO production were examined. These mice developed marked granulomatous, but not necrotic, lesions in their lungs and spleens. Compared with the levels in wild-type mice, the splenic IFN-gamma levels were low but the IL-12 levels were normal in IL-18-deficient mice. The reduced IFN-gamma production was not secondary to reduced induction of IL-12 production. The levels of NO production by peritoneal macrophages of IL-18-deficient and wild-type mice did not differ significantly. Granulomatous lesion development by IL-18-deficient mice was inhibited significantly by treatment with exogenous recombinant IL-18, Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-gamma expression.