Interleukin-18 (IL-18) enhances innate IL-12-mediated resistance to Toxoplasma gondii
Interleukin-18 (IL-18) enhances innate IL-12-mediated resistance to Toxoplasma gondii
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DOI：
10.1128/iai.68.12.6932-6938.2000
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发表时间：
2000-12-01
影响因子：
3.1
通讯作者：
Hunter, CA
中科院分区：
文献类型：
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作者：
Cai, GF;Kastelein, R;Hunter, CA
对弓形虫的天然抗性依赖于白细胞介素-12（IL-12）刺激自然杀伤（NK）细胞产生γ干扰素（IFN-γ）的能力。由于IL-18是IL-12诱导的NK细胞产生IFN-γ的有效增强剂，因此使用缺乏适应性免疫应答的SCID小鼠来评估IL-18在对T细胞的先天抗性中的作用。刚地。对感染T.弓形虫导致血清IFN-γ水平的早期降低，但没有显著降低对这种感染的抵抗力。相比之下，给受感染的SCID小鼠施用外源性IL-18导致IFN-γ产生增加，寄生虫负担减少，死亡时间延迟。IL-18治疗的保护作用与局部给药部位的NK细胞数量和细胞毒性活性增加以及治疗小鼠脾脏中诱导型一氧化二氮合成酶水平升高相关。此外，体内耗竭研究表明，外源性IL-18增强T.弓形虫依赖于IL-12、IFN-γ和NK细胞。总之，这些研究表明，虽然内源性IL-18似乎在先天性T细胞抗性中的作用有限。用IL-18处理可以增强NK细胞介导的对该病原体的免疫。
Innate resistance to Toxoplasma gondii is dependent on the ability of interleukin-12 (IL-12) to stimulate natural killer (NK) cell production of gamma interferon (IFN-gamma). Since IL-18 is a potent enhancer of IL-12-induced production of IFN-gamma by NK cells, SCID mice which lack an adaptive immune response) were used to assess the role of IL-18 in innate resistance to T. gondii. Administration of anti-IL-18 to SCID mice infected with T. gondii resulted in an early reduction in serum levels of IFN-gamma but did not significantly decrease resistance to this infection. In contrast, administration of exogenous IL-18 to infected SCID mice resulted in increased production of IFN-gamma, reduced parasite burden, and a delay in time to death. The protective effects of IL-18 treatment correlated with increased NK cell numbers and cytotoxic activity at the local site of administration and with elevated levels of inducible nitrous oxide synthose in the spleens of treated mice. In addition, in vivo depletion studies demonstrated that the ability of exogenous IL-18 to enhance resistance to T. gondii was dependent on IL-12, IFN-gamma, and NK cells. Together, these studies demonstrate that although endogenous IL-18 appears to have a limited role in innate resistance to T. gondii, treatment with IL-18 can augment NK cell-mediated immunity to this pathogen.