Decreased susceptibility of mice to infection with Listeria monocytogenes in the absence of interleukin-18
Decreased susceptibility of mice to infection with Listeria monocytogenes in the absence of interleukin-18
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DOI：
10.1128/iai.01651-07
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发表时间：
2008-09-01
影响因子：
3.1
通讯作者：
Foerster, Irmgard
中科院分区：
文献类型：
--
作者：
Lochner, Matthias;Kastenmueller, Kathrin;Foerster, Irmgard
促炎细胞因子如γ干扰素（ifn - γ）和肿瘤坏死因子α的诱导对于细菌感染的早期控制至关重要。由于白细胞介素-18 （IL-18）作为ifn - γ的有效诱导剂，它可能在李斯特菌病中诱导保护性免疫反应中发挥重要作用。我们使用小鼠单细胞增生李斯特菌感染模型来研究在缺乏IL-18的情况下对这些细胞内细菌的免疫反应。为此，将il -18缺陷小鼠和抗il -18中和抗体处理的小鼠感染单核细胞增生乳杆菌，并将其先天和适应性免疫反应与对照小鼠进行比较。出乎意料的是，我们发现缺乏IL-18的小鼠对单核增生乳杆菌的原发感染具有部分抗性。感染后第3天，对照组小鼠肝脏和脾脏中的李斯特菌数量比il -18缺乏或抗il -18抗体处理的小鼠高500倍。此外，il -18缺失小鼠的促炎细胞因子水平明显降低。感染后48 ~ 72 h， il -18缺陷小鼠对单核增生乳杆菌感染的抵抗力增强，脾脏白细胞数量增加，细胞凋亡减少。相比之下，对照组和il -18缺陷小鼠在产生单核细胞增生乳杆菌特异性t细胞反应的能力上没有显着差异。
The induction of proinflammatory cytokines such as gamma interferon (IFN-gamma) and tumor necrosis factor alpha is crucial for the early control of bacterial infections. Since interleukin-18 (IL-18) acts as a potent inducer of IFN-gamma, it might play an important role in the induction of a protective immune response in listeriosis. We used a murine model of systemic Listeria monocytogenes infection to study the immune response to these intracellular bacteria in the absence of IL-18. For this purpose, IL-18-deficient mice and mice treated with anti-IL-18 neutralizing antibody were infected with L. monocytogenes, and their innate and adaptive immune responses were compared to those of control mice. Unexpectedly, we found that mice deficient in IL-18 were partially resistant to primary infection with L. monocytogenes. At day 3 after infection, the numbers of listeriae in the livers and spleens of control mice were up to 500 times higher than those in IL-18-deficient or anti-IL-18 antibody-treated mice. In addition, the level of proinflammatory cytokines was markedly reduced in IL-18-deficient mice. Enhanced resistance to L. monocytogenes infection in IL-18-deficient mice was accompanied by increased numbers of leukocytes and reduced apoptosis in the spleen 48 to 72 h after infection. In contrast, control and IL-18-deficient mice showed no significant differences in their abilities to mount a protective L. monocytogenes-specific T-cell response.