Interleukin-17A mediates acquired immunity to pneumococcal colonization.
Interleukin-17A mediates acquired immunity to pneumococcal colonization.
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白介素17a介导获得的对肺炎球菌定殖的免疫力。
DOI：
10.1371/journal.ppat.1000159
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发表时间：
2008-09-19
期刊：
影响因子：
6.7
通讯作者：
Malley, Richard
中科院分区：
文献类型：
--
作者：
Lu, Ying-Jie;Gross, Jane;Bogaert, Debby;Finn, Adam;Bagrade, Linda;Zhang, Qibo;Kolls, Jay K.;Srivastava, Amit;Lundgren, Anna;Forte, Sophie;Thompson, Claudette M.;Harney, Kathleen F.;Anderson, Porter W.;Lipsitch, Marc;Malley, Richard
虽然抗荚膜抗体赋予肺炎球菌的亚型特异性免疫，但儿童在这些抗体出现之前清除定植的能力增加，这表明涉及其他机制。我们以前报道过，小鼠鼻内免疫肺炎球菌赋予CD 4 + T细胞依赖性，抗体和抗体型独立的保护，防止殖民。在这里，我们表明，这种免疫力，而不是防止开始携带，加速清除数天，伴随着鼻咽粘膜的嗜中性粒细胞浸润。免疫CD 4 + T细胞的连续转移足以赋予幼稚RAG 1 −/−小鼠免疫力。白细胞介素（IL）-17 A的关键作用得到证实：缺乏干扰素-γ或IL-4的小鼠受到保护，但缺乏IL-17 A受体的小鼠或中性粒细胞耗竭的小鼠则没有受到保护。测定了响应于肺炎球菌的IL-17 A的体外表达：来自接种疫苗的小鼠的淋巴组织比对照组表达显著更多的IL-17 A，并且来自免疫小鼠的外周血样品的IL-17 A表达预测了体内保护。IL-17 A引起的肺炎球菌刺激扁桃体细胞的儿童或成人血液，但不是脐带血。在不存在和存在抗体和补体的情况下，IL-17 A都增加了人类中性粒细胞对肺炎球菌的杀伤作用。我们的结论是，IL-17 A介导的肺炎球菌免疫小鼠，可能在人类，其在体外诱导可能有助于候选肺炎球菌疫苗的发展。肺炎链球菌（肺炎球菌）在儿童和老年人中引起严重疾病，包括肺炎和脑膜炎（大脑炎症）。在鼻子中携带肺炎球菌是大多数感染的必要的第一步。随着儿童年龄的增长，他们携带肺炎球菌的时间更短，患病的风险也会降低。这种与年龄有关的携带率下降的机制尚不清楚。更深入地了解对定植的抗性将使我们能够开发更好的肺炎球菌疫苗。使用实验小鼠模型，我们表明，反复暴露于肺炎球菌导致随后的肺炎球菌携带持续时间的减少，类似于在人类中观察到的。我们确定了负责这一过程的免疫细胞，即所谓的TH 17细胞，它释放一种因子，使人类血细胞能够更有效地杀死肺炎球菌。我们发现这些TH 17细胞存在于成人和儿童中，但不存在于新生儿中，这表明它们可能是人类暴露于肺炎球菌的结果。我们描述了一种用于测量人体中这些细胞的测定法。这种检测方法可以促进针对肺炎球菌携带的新型疫苗的开发。
Although anticapsular antibodies confer serotype-specific immunity to pneumococci, children increase their ability to clear colonization before these antibodies appear, suggesting involvement of other mechanisms. We previously reported that intranasal immunization of mice with pneumococci confers CD4+ T cell–dependent, antibody- and serotype-independent protection against colonization. Here we show that this immunity, rather than preventing initiation of carriage, accelerates clearance over several days, accompanied by neutrophilic infiltration of the nasopharyngeal mucosa. Adoptive transfer of immune CD4+ T cells was sufficient to confer immunity to naïve RAG1−/− mice. A critical role of interleukin (IL)-17A was demonstrated: mice lacking interferon-γ or IL-4 were protected, but not mice lacking IL-17A receptor or mice with neutrophil depletion. In vitro expression of IL-17A in response to pneumococci was assayed: lymphoid tissue from vaccinated mice expressed significantly more IL-17A than controls, and IL-17A expression from peripheral blood samples from immunized mice predicted protection in vivo. IL-17A was elicited by pneumococcal stimulation of tonsillar cells of children or adult blood but not cord blood. IL-17A increased pneumococcal killing by human neutrophils both in the absence and in the presence of antibodies and complement. We conclude that IL-17A mediates pneumococcal immunity in mice and probably in humans; its elicitation in vitro could help in the development of candidate pneumococcal vaccines. The bacterium Streptococcus pneumoniae (pneumococcus) causes serious disease in children and the elderly, including pneumonia and meningitis (inflammation of the brain). Carriage of pneumococcus in the nose is a necessary first step for most infections. As children age, they carry pneumococcus for shorter periods of time and their risk of disease decreases also. The mechanisms underlying this age-related decrease of carriage are not well understood. A deeper understanding of resistance to colonization would enable us to develop better pneumococcal vaccines. Using experimental mouse models, we show that repeated exposure to pneumococci leads to a subsequent reduction in duration of pneumococcal carriage, similar to what is observed in humans. We identify the immune cells that are responsible for this process, so-called TH17 cells, which release a factor that enables human blood cells to kill pneumococcus more efficiently. We show that these TH17 cells exist in adults and children, but not in newborn babies, which suggests that they may arise as a consequence of humans being exposed to pneumococcus. We describe an assay for the measurement of these cells in humans. Such an assay could facilitate the development of novel vaccines directed against pneumococcal carriage.
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影响因子：
3.6
作者：
Black, S;Shinefield, H;Edwards, K
通讯作者：
Edwards, K
影响因子：
3.1
作者：
Basset, Alan;Thompson, Claudette M.;Malley, Richard
通讯作者：
Malley, Richard
影响因子：
11.8
作者：
Dworkin, MS;Ward, JW;Kaplan, JE
通讯作者：
Kaplan, JE
DOI：
10.1073/pnas.0501254102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Malley, R;Trzcinski, K;Lipsitch, M
通讯作者：
Lipsitch, M
影响因子：
15.8
作者：
Lipsitch M;Whitney CG;Zell E;Kaijalainen T;Dagan R;Malley R
通讯作者：
Malley R