IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice
IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice
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DOI：
10.4049/jimmunol.168.3.1348
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发表时间：
2002-02-01
影响因子：
4.4
通讯作者：
Stevenson, MM
中科院分区：
文献类型：
--
作者：
Su, Z;Stevenson, MM
在这项研究中，我们研究了内源性IL-12的作用，在保护性免疫对血液阶段的夏氏疟原虫AS疟疾使用IL-12 p40基因敲除（KO）和野生型（WT）C57 BL/6小鼠。感染后，KO小鼠的原发性寄生虫血症水平显著高于WT小鼠，并且不能快速解决原发性感染和控制攻毒感染。与WT小鼠相比，感染的KO小鼠体内和体外NK细胞和脾细胞的IFN-γ产生严重受损。在感染的KO小鼠中，TNF-α和IL-4的产生没有受到损害。KO小鼠产生的Th 1-依赖性IgG 2a和IgG 3的水平显着较低，但较高的Th 2-依赖性IgG 1的水平比WT小鼠在原发性和挑战感染。在原发感染的早期阶段用鼠rIL-12治疗KO小鼠，纠正了改变的IgG 2a、IgG 3和IgG 1应答，并恢复了快速解决原发感染和对照攻毒感染的能力。将免疫血清从WT小鼠转移到夏氏疟原虫AS感染的易感A/J小鼠完全保护了受体，而来自KO小鼠的免疫血清则没有，如受体小鼠中高水平的寄生虫血症和100%死亡率所证明的。此外，WT免疫血清中IgG 2a的消耗显著降低了血清的保护作用，而IgG 1消耗没有显著影响。两者合计，这些结果表明，在血液阶段疟疾的急性和慢性阶段的Th 1-免疫应答的保护作用，并延长IL-12的免疫调节作用，抗体介导的免疫疟原虫寄生虫。
In this study, we investigated the role of endogenous IL-12 in protective immunity against blood-stage P. chabaudi AS malaria using IL-12 p40 gene knockout (KO) and wild-type (WT) C57BL/6 mice. Following infection, KO mice developed significantly higher levels of primary parasitemia than WT mice and were unable to rapidly resolve primary infection and control challenge infection. Infected KO mice had severely impaired IFN-gamma production in vivo and in vitro by NK cells and splenocytes compared with WT mice. Production of TNF-alpha and IL-4 was not compromised in infected KO mice. KO mice produced significantly lower levels of Th1-dependent IgG2a and IgG3 but a higher level of Th2-dependent IgG1 than WT mice during primary and challenge infections. Treatment of KO mice with murine rIL-12 during the early stage of primary infection corrected the altered IgG2a, IgG3, and IgG1 responses and restored the ability to rapidly resolve primary and control challenge infections. Transfer of immune serum from WT mice to P. chabaudi AS-infected susceptible A/J mice completely protected the recipients, whereas immune serum from KO mice did not, as evidenced by high levels of parasitemia and 100% mortality in recipient mice. Furthermore, depletion of IgG2a from WT immune serum significantly reduced the protective effect of the serum while IgG1 depletion had no significant effect. Taken together, these results demonstrate the protective role of a Th1-immune response during both acute and chronic phases of blood-stage malaria and extend the immunoregulatory role of IL-12 to Ab-mediated immunity against Plasmodium parasites.