The complexity of protective immunity against liver-stage malaria
The complexity of protective immunity against liver-stage malaria
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DOI：
10.4049/jimmunol.165.3.1453
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发表时间：
2000-08-01
影响因子：
4.4
通讯作者：
Hoffman, SL
中科院分区：
文献类型：
--
作者：
Doolan, DL;Hoffman, SL
抗疟原虫攻击的无菌保护性免疫，子孢子可在多种模型系统和人类中通过辐射减毒的疟原虫子孢子免疫诱导。感染的肝细胞已被确定为这种保护的主要靶点，但其潜在的机制尚未完全明确。ABS、CD8(+)T细胞、CD4(+)T细胞、细胞因子(包括干扰素-γ和IL-12)和NO都被认为是关键效应因子。在这里，我们研究了不同的疫苗递送系统(辐照的子孢子、质粒DNA、合成肽/佐剂和多个Ag肽)免疫在遗传不同的近交系、转基因小鼠和近交系小鼠中诱导保护性免疫的机制。我们发现存在显著差异的T细胞依赖的免疫反应，它们介导对肝期疟疾的无菌保护性免疫，此外，我们还证明了不同品系的近交系小鼠通过单一免疫方法诱导不同的保护机制，而同一品系的小鼠通过不同的免疫方法诱导不同的保护机制。这些数据突显了小鼠宿主对寄生虫感染反应的复杂性，并表明远亲繁殖的人类群体可能会有类似的行为。然而，数据表明，应设计一种红细胞前期疫苗来诱导CD8(+)T细胞和干扰素-γ介导的免疫反应，而干扰素-γ反应可能代表了红细胞前期保护性免疫的体外相关性。
Sterile protective immunity against challenge with Plasmodium spp, sporozoites can be induced in multiple model systems and humans by immunization with radiation-attenuated Plasmodium spp, sporozoites. The infected hepatocyte has been established as the primary target of this protection, but the underlying mechanisms have not been completely defined. Abs, CD8(+) T cells, CD4(+) T cells, cytokines (including IFN-gamma and IL-12), and NO have all been implicated as critical effecters. Here, we have investigated the mechanisms of protective immunity induced by immunization with different vaccine delivery systems (irradiated sporozoites, plasmid DNA, synthetic peptide/adjuvant, and multiple Ag peptide) in genetically distinct inbred strains, genetically modified mice, and outbred mice. We establish that there is a marked diversity of T cell-dependent immune responses that mediate sterile protective immunity against Liver-stage malaria, Furthermore, we demonstrate that distinct mechanisms of protection are induced in different strains of inbred mice by a single method of immunization, and in the same strain by different methods of immunization. These data underscore the complexity of the murine host response to a parasitic infection and suggest that an outbred human population may behave similarly. Data nevertheless suggest that a pre-erythrocytic-stage vaccine should be designed to induce CD8(+) T cell- and IFN-gamma-mediated immune responses and that IFN-gamma responses may represent an in vitro correlate of pre-erythrocytic-stage protective immunity.