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Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi

机译:暴露于婴儿利什曼原虫chagasi的巴西周边城市人口对新抗原的细胞因子反应。

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摘要

Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process. We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania-specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts. Magnitude of DTH correlated with crude Leishmania antigen–driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients. The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36–71% of responders) in recovered VL patients and DTH+ persons. This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates.
机译:如果不治疗,内脏利什曼病(VL)会致命,并且没有针对该疾病的疫苗。在低水平的白介素10(IL-10)存在下,高水平的CD4衍生干扰素-γ(IFN-γ)可以预测疫苗的成功。肿瘤坏死因子-α(TNF-α)在此过程中也很重要。我们在暴露于巴西婴儿利什曼原虫的三组患者中表征了人类免疫反应:1)药物治疗的VL患者(恢复的VL); 2)利什曼原虫特异性迟发型超敏反应皮肤反应(DTH +)阳性的无症状者; 3)DTH阴性家庭接触者。 DTH的大小与利什曼原虫抗原驱动的IFN-γ,TNF-α和IL-5(而非IL-10)有关。与康复的VL患者相比,DTH +患者显示出与胰蛋白酶2过氧化物酶和激活的C激酶受体的利什曼原虫同源物相当的IFN-γ水平,但更高的IL-10水平。 VL患者中IFN-γ:IL-10和TNF-α:IL-10的比率高于DTH +患者。 11名新候选人中的7名(R71,L37,N52,L302.06,M18,J41和M22)在恢复的VL患者和DTH +患者中引起细胞因子应答(应答者的36–71%)。该结果证实了其作为跨物种疫苗/免疫治疗候选物的推定地位。

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