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首页> 外文期刊>Frontiers in Immunology >F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis
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F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis

机译:利什曼原虫(Leishmania)donovani 核苷水解酶的F1域促进 Leishmania(Leishmania)babyum 治愈的患者和生活在利什曼病流行地区的无症状个体的Th1反应。

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摘要

The Leishmania (Leishmania) donovani nucleoside hydrolase NH36 is the main antigen of the Leishmune~(?)vaccine and one of the promising candidates for vaccination against visceral leishmaniasis. The antigenicity of the N-terminal (F1), the central (F2), or the C-terminal recombinant domain (F3) of NH36 was evaluated using peripheral blood mononuclear cells (PBMC) from individuals infected with L. (L.) infantum from an endemic area of visceral leishmaniasis of Spain. Both NH36 and F1 domains significantly increased the PBMC proliferation stimulation index of cured patients and infected asymptomatic individuals compared to healthy controls. Moreover, F1 induced a 19% higher proliferative response than NH36 in asymptomatic exposed subjects. In addition, in patients cured from visceral leishmaniasis, proliferation in response to NH36 and F1 was accompanied by a significant increase of IFN-γ and TNF-α secretion, which was 42–43% higher, in response to F1 than to NH36. The interleukin 17 (IL-17) secretion was stronger in asymptomatic subjects, in response to F1, as well as in cured cutaneous leishmaniasis after NH36 stimulation. While no IL-10 secretion was determined by F1, a granzyme B increase was detected in supernatants from cured patients after stimulation with either NH36 or F1. These data demonstrate that F1 is the domain of NH36 that induces a recall cellular response in individuals with acquired resistance to the infection by L. (L.) infantum . In addition, F1 and NH36 discriminated the IgG3 humoral response in patients with active visceral leishmaniasis due to L. (L.) donovani (Ethiopia) and L. (L.) infantum (Spain) from that of endemic and non-endemic area controls. NH36 showed higher reactivity with sera from L. (L.) donovani -infected individuals, indicating species specificity. We conclude that the F1 domain, previously characterized as an inducer of the Th1 and Th17 responses in cured/exposed patients infected with L. (L.) infantum chagasi , may also be involved in the generation of a protective response against L. (L.) infantum and represents a potential vaccine candidate for the control of human leishmaniasis alone, or in combination with other HLA epitopes/antigens.
机译:利什曼原虫(Leishmania)donovani核苷水解酶NH36是利什曼疫苗的主要抗原,也是针对内脏利什曼病的有希望的疫苗之一。 NH36的N末端(F1),中央(F2)或C末端重组结构域(F3)的抗原性使用来自婴儿L.(L.)感染个体的外​​周血单核细胞(PBMC)进行评估来自西班牙内脏利什曼病的流行地区。与健康对照组相比,NH36和F1结构域均显着提高了治愈患者和感染无症状个体的PBMC增殖刺激指数。此外,在无症状暴露的受试者中,F1引起的增殖反应比NH36高19%。此外,在内脏利什曼病治愈的患者中,对NH36和F1的应答增殖伴随着IFN-γ和TNF-α分泌的显着增加,对F1的应答比对NH36的应答高42-43%。在无症状的受试者中,对F1的响应以及在NH36刺激后治愈的皮肤利什曼病中的白细胞介素17(IL-17)分泌均较强。尽管F1不能确定IL-10的分泌,但是在用NH36或F1刺激后,治愈患者的上清液中却检测到了颗粒酶B的增加。这些数据表明,F1是NH36的结构域,在具有对婴儿L.(L.)感染的抵抗力的个体中,可诱导召回细胞应答。此外,F1和NH36区分活动性内脏利什曼病的IgG3体液反应是由于L.(L.)donovani(埃塞俄比亚)和L.(L.)babyum(L.)babyum(西班牙)与地方病区和非地方病区对照所致。 NH36与来自多巴尼酵母(L.)的个体的血清显示出更高的反应性,表明物种特异性。我们得出的结论是,以前被表征为感染婴儿L.(L。)婴儿的治愈/暴露的患者中Th1和Th17反应的诱导物的F1结构域也可能参与了针对L.(L 。)婴儿,代表单独或与其他HLA表位/抗原联合控制人利什曼病的潜在疫苗候选者。

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