An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis.
An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis.
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DOI：
10.1371/journal.pone.0106426
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Jones DE
中科院分区：
文献类型：
--
作者：
Gibson-Corley KN;Bockenstedt MM;Li H;Boggiatto PM;Phanse Y;Petersen CA;Bellaire BH;Jones DE
C3HeB/FeJ小鼠脚垫感染亚马孙利什曼原虫导致慢性病变，伴有大量寄生虫负荷。与L. major共同感染这些动物导致诱导有效的Th1免疫反应，可以解决这些病变。这种交叉保护可以在体外重现，利用大乳杆菌感染动物的免疫细胞有效激活亚马逊乳杆菌感染的巨噬细胞来杀死寄生虫。我们之前已经证明，B细胞群及其IgG2a抗体是有效交叉保护所必需的。在这里，我们证明，与L. major相反，杀死亚马逊L.寄生虫依赖于感染巨噬细胞的FcRγ共链和NADPH氧化酶产生的超氧化物。在激活后5天，超氧化物的产生与亚马孙乳杆菌的杀伤一致，这表明寄生虫的opsonization不可能是抗体反应的机制。因此，我们验证了非特异性免疫复合物可能提供FcRγ共链/NADPH氧化酶依赖性寄生虫杀伤机制的假设。可溶性IgG2a免疫复合物、IFN-γ和寄生虫抗原激活巨噬细胞可显著降低亚马逊河蛭感染巨噬细胞的百分比。这些结果确定了在利什曼原虫感染期间有效的宿主保护机制，并首次证明了IgG抗体可以增强细胞内病原体杀伤的新方法。
Footpad infection of C3HeB/FeJ mice with Leishmania amazonensis leads to chronic lesions accompanied by large parasite loads. Co-infecting these animals with L. major leads to induction of an effective Th1 immune response that can resolve these lesions. This cross-protection can be recapitulated in vitro by using immune cells from L. major-infected animals to effectively activate L. amazonensis-infected macrophages to kill the parasite. We have shown previously that the B cell population and their IgG2a antibodies are required for effective cross-protection. Here we demonstrate that, in contrast to L. major, killing L. amazonensis parasites is dependent upon FcRγ common-chain and NADPH oxidase-generated superoxide from infected macrophages. Superoxide production coincided with killing of L. amazonensis at five days post-activation, suggesting that opsonization of the parasites was not a likely mechanism of the antibody response. Therefore we tested the hypothesis that non-specific immune complexes could provide a mechanism of FcRγ common-chain/NADPH oxidase dependent parasite killing. Macrophage activation in response to soluble IgG2a immune complexes, IFN-γ and parasite antigen was effective in significantly reducing the percentage of macrophages infected with L. amazonensis. These results define a host protection mechanism effective during Leishmania infection and demonstrate for the first time a novel means by which IgG antibodies can enhance killing of an intracellular pathogen.
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影响因子：
5.8
作者：
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通讯作者：
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