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首页> 美国卫生研究院文献>Oncotarget >Characterization of a secreted macrophage migration inhibitory factor homologue of the parasitic nematode Haemonchus Contortus acting at the parasite-host cell interface
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Characterization of a secreted macrophage migration inhibitory factor homologue of the parasitic nematode Haemonchus Contortus acting at the parasite-host cell interface

机译：寄生虫-宿主细胞界面上的寄生线虫Haemonchus Contortus分泌的巨噬细胞迁移抑制因子同源物的表征

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摘要

Modulation and suppression of the immune response of the host by nematode parasites have been reported extensively and the migration inhibitory factor (MIF) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant MIF protein from the small ruminant’s nematode parasite Haemonchus contortus (rHCMIF-1), and investigated its immunomodulatory effects on goat monocyte. Enzymatic assays indicated that rHCMIF-1 possessed tautomerase activity. Immunohistochemical test demonstrated that the native HCMIF-1 protein was predominantly localized at the body surface and internal surface of the worm’s gut. We demonstrated that rHCMIF-1 could be distinguished by antisera from goats experimentally infected with H. contortus and could bind by goat monocytes. The immunomodulatory effects of HCMIF-1 on cytokine secretion, MHC molecule expression, NO production and phagocytosis were observed by co-incubation of rHCMIF-1 with goat monocytes. The results showed that the interaction of rHCMIF-1 decreased the production of TNF-α, IL-1β and IL-12p40, where as, it significantly increased the secretion of IL-10 and TGF β in goat monocytes. After rHCMIF-1 exposure, the expression of MHC-II on goat monocytes was inhibited. Moreover, rHCMIF-1 could down-regulate the LPS induced NO production of goat monocytes. Phagocytotic assay by FITC-dextran internalization showed that rHCMIF-1 could inhibit the phagocytosis of goat monocytes. Our findings provided potential targetas immunoregulator, and will be helpful to elucidate the molecular basis of host–parasite interactions and search for new potential protein as vaccine and drug target candidate.
机译：线虫寄生虫对宿主免疫应答的调节和抑制已被广泛报道，并且迁移抑制因子（MIF）被确定为主要的免疫调节剂之一。在本研究中，我们从小型反刍动物的线虫寄生弯曲杆菌Haemonchus contortus（rHCMIF-1）克隆并生产了重组MIF蛋白，并研究了其对山羊单核细胞的免疫调节作用。酶促测定表明rHCMIF-1具有互变异构酶活性。免疫组织化学测试表明，天然HCMIF-1蛋白主要位于蠕虫肠道的体表和内表面。我们证明，rHCMIF-1可以通过抗血清与实验性感染了弯曲杆菌的山羊区分开，并且可以被山羊单核细胞结合。通过将rHCMIF-1与山羊单核细胞共孵育，观察到HCMIF-1对细胞因子分泌，MHC分子表达，NO产生和吞噬作用的免疫调节作用。结果表明，rHCMIF-1的相互作用减少了TNF-α，IL-1β和IL-12p40的产生，因此，它显着增加了山羊单核细胞IL-10和TGFβ的分泌。暴露于rHCMIF-1后，山羊单核细胞MHC-II的表达受到抑制。此外，rHCMIF-1可能下调LPS诱导的山羊单核细胞NO生成。 FITC-葡聚糖内化作用的吞噬作用分析表明，rHCMIF-1可以抑制山羊单核细胞的吞噬作用。我们的发现提供了潜在的靶标免疫调节剂，将有助于阐明宿主与寄生虫相互作用的分子基础，并寻找新的潜在蛋白作为疫苗和药物靶标候选物。

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