Th17 responses to pneumococcus in blood and adenoidal cells in children.
Th17 responses to pneumococcus in blood and adenoidal cells in children.
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Th17 对儿童血液和腺样细胞中肺炎球菌的反应。
DOI：
10.1111/cei.13225
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发表时间：
2019
影响因子：
4.6
通讯作者：
Oliver E
中科院分区：
文献类型：
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作者：
Oliver E
肺炎球菌感染造成了巨大的全球健康负担，寻找非血清型疫苗的工作仍在继续。现有的结合疫苗通过靶向血清型减少鼻咽定植。新抗原的这种粘膜效应也同样重要。已经在小鼠中描述了CD4+Th17细胞依赖、抗体非依赖的定植减少和增强清除。在这里，我们描述了在人类细胞培养中，使用腺样体和外周血单核细胞来评估T辅助类型17(Th17)细胞因子对候选肺炎球菌蛋白疫苗抗原的反应。在这些原代细胞培养中，IL-17A的最佳检测时间为第7天，IL-22的最佳检测时间为第11天。去除CD45RO+记忆T细胞可消除这些反应。在腺样体细胞中，IL-17A的反应量随年龄的增加而明显增加，但IL-22的反应量没有明显的变化。肺炎球菌抗原刺激后个体IL-17A和IL-22的反应有很强的相关性(P<；0·015)。经佛波酯/离子霉素刺激后的细胞内细胞因子染色显示，30%IL-22阳性的T细胞表达γδT细胞受体和/或CD56，而IL-17A+细胞的比例较低(P<；0.001)。观察到了对几种候选疫苗抗原的反应，但对PhtD(P<；0.0001)一直缺乏反应，尤其是在血液中，PhtD(P<；0.0001)是一种最近在婴儿中进行的含PhtD结合疫苗的临床试验中被证明不会影响定植的抗原。所提供的数据和讨论的方法有可能有助于识别旨在减少肺炎球菌携带和传播的新型疫苗抗原，从而改进经验临床试验的设计。
Pneumococcal infections cause a large global health burden, and the search for serotype-independent vaccines continues. Existing conjugate vaccines reduce nasopharyngeal colonization by target serotypes. Such mucosal effects of novel antigens may similarly be important. CD4+Th17 cell-dependent, antibody-independent reductions in colonization and enhanced clearance have been described in mice. Here we describe the evaluation of T helper type 17 (Th17) cytokine responses to candidate pneumococcal protein vaccine antigens in human cell culture, using adenoidal and peripheral blood mononuclear cells. Optimal detection of interleukin (IL)-17A was at day 7, and of IL-22 at day 11, in these primary cell cultures. Removal of CD45RO+memory T cells abolished these responses. Age-associated increases in magnitude of responses were evident for IL-17A, but not IL-22, in adenoidal cells. There was a strong correlation between individual IL-17A and IL-22 responses after pneumococcal antigen stimulation (P< 0·015). Intracellular cytokine staining following phorbol myristate acetate (PMA)/ionomycin stimulation demonstrated that > 30% CD4+T cells positive for IL-22 express the innate markers γδT cell receptor and/or CD56, with much lower proportions for IL-17A+cells (P< 0·001). Responses to several vaccine candidate antigens were observed but were consistently absent, particularly in blood, to PhtD (P< 0·0001), an antigen recently shown not to impact colonization in a clinical trial of a PhtD-containing conjugate vaccine in infants. The data presented and approach discussed have the potential to assist in the identification of novel vaccine antigens aimed at reducing pneumococcal carriage and transmission, thus improving the design of empirical clinical trials.