Genetically resistant mice lacking IL-18 gene develop Th1 response and control cutaneous Leishmania major infection
Genetically resistant mice lacking IL-18 gene develop Th1 response and control cutaneous Leishmania major infection
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DOI：
10.4049/jimmunol.164.11.5890
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发表时间：
2000-06-01
影响因子：
4.4
通讯作者：
Satoskar, AR
中科院分区：
文献类型：
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作者：
Monteforte, GM;Takeda, K;Satoskar, AR
IL-18已被证明在Th 1应答和针对细胞内病原体的免疫的发展中起关键作用。为了确定IL-18在抗硕大利什曼原虫保护性免疫发展中的作用，我们分析了皮肤利什曼原虫感染的过程。与类似感染的野生型小鼠（IL-18（+/+））相比，IL-18缺陷型C57 BL/6小鼠（IL-18（-/-））中的主要差异。继L.在严重感染的情况下，IL-18（-/-）小鼠在感染的早期阶段可能产生更大的病变，但最终将与IL-18（+/+）小鼠一样有效地解决它们。感染后2 wk，尽管Ag刺激的L. IL-18（+/+）和IL-18（-/-）小鼠产生的IFN-γ水平相似，IL-18（-/-）小鼠产生的IL-12和IL-4水平显著高于IL-18（+/+）和IL-18（-/-）小鼠。此时，来自IL-18（+/+）和IL-18（-/-）小鼠的淋巴结细胞产生IL-12和IFN-γ，但不产生IL-4。少校这些结果表明，尽管IL-18可能在早期控制皮肤L。主要损伤生长，这种细胞因子对于保护性Thl应答的发展和L.严重感染
IL-18 has been shown to play a critical role in the development of a Th1 response and immunity against intracellular pathogens. To determine the role of IL-18 in the development of protective immunity against Leishmania major,we have analyzed the course of cutaneous L. major in IL-18-deficient C57BL/6 mice (IL-18(-/-)) compared with similarly infected wild-type mice (IL-18(+/+)). After L. major infection, IL-18(-/-) mice may develop larger lesions during eariy phase of infection,but eventually will resolve them as efficiently as IL-18(+/+) mice. By 2 wk after infection, although Ag-stimulated lymph nude cells from L. major-infected IL-18(+/+) and IL-18(-/-) mice produced similar levels of IFN-gamma, those from IL-18(-/-) mice produced significantly more IL-12 and IL-4, By 10 wk after infection, both IL-18(+/+) and IL-18(-/-) mice had resolved L. major infection, At this time, lymph node cells from both IL-18(+/+) and IL-18(-/-) mice produced IL-12 and IFN-gamma but no IL-4, Furthermore, administration of anti-IFN-gamma Abs to IL-18(-/-) mice rendered them susceptible to L. major. These results indicate that despite the role IL-18 may play in early control of cutaneous L. major lesion growth, this cytokine is not critical for development of protective Thl response and resolution of L. major infection.