Characterization of Th17 responses to Streptococcus pneumoniae in humans: Comparisons between adults and children in a developed and a developing country
Characterization of Th17 responses to Streptococcus pneumoniae in humans: Comparisons between adults and children in a developed and a developing country
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DOI：
10.1016/j.vaccine.2012.03.082
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发表时间：
2012-06-06
期刊：
影响因子：
5.5
通讯作者：
Malley, Richard
中科院分区：
文献类型：
--
作者：
Lundgren, Anna;Bhuiyan, Taufiqur R.;Malley, Richard
鼻内暴露于肺炎链球菌以及用最近开发的灭活肺炎球菌全细胞疫苗进行粘膜或肠胃外免疫，赋予Th 17介导的针对随后的S.小鼠中的肺炎定殖。鉴于我们对Th 17细胞功能的兴趣以及正在努力开发这种疫苗用于发展中国家的婴儿和儿童，我们分析了健康个体和肺炎球菌疾病患者对全细胞抗原（WCA）和单个肺炎球菌抗原的Th 17应答，并比较了瑞典和孟加拉国儿童和成人的应答。从瑞典成人分离的外周血单核细胞（PBMC）在用WCA、肺炎链球菌PdT和B组链球菌（Pcs B）中细胞分离所需的蛋白质刺激后产生IL-17 A。还检测到IL-22和IFN-γ应答，但这些细胞因子来源于不同的CD 4 +T细胞亚群。与成人相比，瑞典儿童的PBMC产生的IL-17 A水平较低，而孟加拉国的样本则没有这种差异，儿童和成人的反应均显着高于瑞典。在经证实或可能患有肺炎球菌性肺炎的儿童中也观察到对WCA刺激的高IL-17 A反应。因此，我们的研究结果表明，在儿童和成人中存在对肺炎球菌具有特异性的Th 17型T细胞。在发展中国家和发达国家，儿童和成人对肺炎球菌的Th 17应答水平不同，这可能至少部分是由于肺炎球菌暴露的差异，这是在人体试验中评价候选肺炎球菌蛋白疫苗时需要考虑的重要因素。(C)2012爱思唯尔有限公司保留所有权利。
Intranasal exposure to Streptococcus pneumoniae as well as mucosal or parenteral immunization with a recently developed killed pneumococcal whole cell vaccine, confer Th17-mediated protection against subsequent S. pneumoniae colonization in mice. Given our interest in the function of Th17 cells and the ongoing efforts to develop this vaccine for use in infants and children in developing countries, we analyzed Th17 responses to the whole cell antigen (WCA) and individual pneumococcal antigens in healthy individuals and patients with pneumococcal disease and compared responses in children and adults from Sweden and Bangladesh. Peripheral blood mononuclear cells (PBMCs) isolated from Swedish adults produced IL-17A after stimulation with WCA, with the pneumolysoid PdT and with the protein required for cell separation in group B streptococci (PcsB). IL-22 and IFN-gamma responses were also detected, but these cytokines originated from separate CD4+T cell subsets. PBMCs from Swedish children produced lower levels of IL-17A in response to WCA compared to adults, whereas no such difference was noted from the samples from Bangladesh, where responses by children and adults were both significantly higher than those in Sweden. High IL-17A responses to stimulation with WCA were also observed in children with proven or probable pneumococcal pneumonia. Our results thus demonstrate the presence of Th17-type T cells that are specific for pneumococcus in both children and adults. The different levels of Th17 responses to pneumococci in children and adults in developing and developed countries, which may at least partly be due to differences in exposure to pneumococci, are important factors to consider in the evaluation of candidate pneumococcal protein-based vaccines in human trials. (C) 2012 Elsevier Ltd. All rights reserved.