Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-β production
Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-β production
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DOI：
10.1016/j.vaccine.2008.04.083
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发表时间：
2008-07-23
期刊：
影响因子：
5.5
通讯作者：
Akuffo, Hannah
中科院分区：
文献类型：
--
作者：
Elias, Daniel;Britton, Sven;Akuffo, Hannah
卡介苗是目前唯一一种在实验动物模型中有效的结核病疫苗，由于其对成人肺结核的疗效不同，长期以来一直受到研究。在这项研究中，我们评估了在接种卡介苗之前进行抗蠕虫治疗是否可以提高蠕虫感染人群接种卡介苗的免疫原性。我们招募了有分枝杆菌感染证据的志愿者，他们是蠕虫的无症状携带者。受试者被随机接受抗寄生虫药物或安慰剂。三个月后，志愿者接种了卡介苗。接种2个月后评估分枝杆菌抗原特异性细胞因子反应。结果发现，与驱虫组相比，安慰剂组的外周血单个核细胞在分枝杆菌抗原混合物(纯化蛋白衍生物)体外刺激下，每2×10(5)个外周血单个核细胞产生干扰素-γ(129vs191，p=0.03)和IL-12(149vs243，p=0.013)的频率较低。另一方面，安慰剂组在PPD(152vs81.3，p=0.002)或T细胞有丝分裂原刀豆蛋白A(210vs157，p=0.03)作用下产生转化生长因子-β细胞的频率更高。然而，当细胞被PPD刺激时，没有观察到产生IL-4或IL-5的细胞。在刀豆蛋白A(IL-4217 vs191，p=0.08)和IL-5(131vs103，p=0.14)刺激下，两组均可诱导出数量相当的细胞因子产生细胞。这里提供的数据表明，慢性蠕虫感染降低了卡介苗在人类中的免疫原性，这与增加转化生长因子-β的产生有关，但与增强的Th2免疫反应无关。(C)2008爱思唯尔有限公司。保留所有权利。
The only vaccine available against tuberculosis (TB), BCG, so effective in experimental animal models, has been under scrutiny for a long time owing to its variable efficacy against pulmonary tuberculosis in adults. In this study, we evaluated whether anti-helminthic therapy prior to BCG vaccination could increase the immunogenicity of BCG vaccination in helminth infected population. We recruited volunteers with evidence of prior mycobacterial infection and who were asymptomatic carriers of helminths. The subjects were randomized to receive either anti-helminthic drugs or placebo. Three months later, BCG vaccination was administered to volunteers. Mycobacterial antigen-specific cytokine responses were assessed 2 months after vaccination. The results show that peripheral blood mononuclear cells obtained from the placebo group were found to have a lower frequency of IFN-gamma (129 vs 191, p=0.03) and IL-12 (149 vs 243, p = 0.013) producing cells per 2 x 10(5) PBMC (peripheral blood mononuclear cells) when stimulated in vitro with a mycobacterial antigen mixture (purified protein derivative (PPD)) compared to those from the dewormed group. On the other hand the placebo group had higher frequency of TGF-beta producing cells in response to PPD (152 vs 81.3, p = 0.002) or the T cell mitogen concanavalin A (Con A) (210 vs 157, p = 0.03). However, no detectable IL-4 or IL-5 producing cells were observed when cells were stimulated with PPD. Comparable numbers of both cytokine producing cells were induced in both groups upon stimulation with concanavalin A (IL-4 217 vs 191, p = 0.08) and IL-5 (131 vs 103, p = 0.14). The data presented here demonstrate that chronic worm infection reduces the immunogenicity of BCG in humans and this was associated with increased TGF-beta production but not with enhanced Th2 immune response. (C) 2008 Elsevier Ltd. All rights reserved.