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PNAS:上海交通大学沈浩研究组揭示辅助性T细胞在抗原识别和疾病保护中的重要作用

2018-07-11 生态平衡 iNature

2018年7月9日,上海交通大学医学院沈浩研究组在PNAS上发表题为“Recognition of conserved antigens by Th17 cells provides broad protection against pulmonary Haemophilus influenzae infection”文章,该文章表明针对肺炎的交叉保护的免疫机制涉及Th17细胞,其响应广谱抗原,包

2018年7月9日,上海交通大学医学院沈浩研究组在PNAS上发表题为“Recognition of conserved antigens by Th17 cells provides broad protection against pulmonary Haemophilus influenzae infection”文章,该文章表明针对肺炎的交叉保护的免疫机制涉及Th17细胞,其响应广谱抗原,包括在NTHi菌株中高度保守的抗原,这些机制表明在亚单位疫苗中包含Th17抗原提供了诱导广泛保护的优势,并补充了目前基于抗体的方法。

不可分型流感嗜血杆菌(NTHi)是社区获得性肺炎和慢性阻塞性肺病恶化的主要原因。 NTHi疫苗开发的当前努力集中于产生针对表面抗原的抗体应答,并且取得了有限的成功,主要是因为许多循环NTHi菌株之间的抗原多样性。在这项研究中,我们已经发现Th17反应作为交叉保护的免疫机制,并识别保守的Th17抗原,并诱导对NTHi肺部感染的保护,因此,关键的第一步是发展一种广泛保护的“通用”疫苗,这是对抗呼吸道病原体疫苗开发的圣杯。

不可分型流感嗜血杆菌(NTHi)是社区获得性肺炎和慢性阻塞性肺病恶化的主要原因。目前NTHi疫苗开发的努力集中于产生体液应答,并且受到许多循环NTHi菌株之间的抗原变异的极大阻碍。在这项研究中,我们发现用灭活的NTHi对小鼠进行肺部免疫可以对不同菌株的肺部感染产生广泛的保护作用。虽然免疫抗体的被动转移仅保护免受同源菌株的侵袭,但免疫T细胞的转移赋予针对同源和异源菌株的保护。进一步的表征揭示了强烈的Th17反应,其与不同的NTHi菌株交叉反应。响应Th17细胞识别细胞溶质和膜相关抗原,而免疫抗体优先响应表面抗原并且具有高度菌株特异性。

研究人员进一步鉴定了在NTHi感染期间肺Th17细胞识别的几种保守蛋白。通过用纯化蛋白质和佐剂免疫小鼠,测试产生最强反应的两种蛋白质作为候选疫苗。免疫诱导的抗原特异性Th17细胞识别不同的菌株,并且在过继转移时赋予保护作用。此外,免疫小鼠不仅受到NTHi菌株的攻击,而且受到完全毒性的包囊菌株的攻击。总之,这些结果表明,针对肺炎的交叉保护的免疫机制涉及Th17细胞,其响应广谱抗原,包括在NTHi菌株中高度保守的抗原。这些机制见解表明,在亚单位疫苗中包含Th17抗原提供了诱导广泛保护的优势,并补充了目前基于抗体的方法。

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    2019-02-28 docwu2019
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    2018-07-24 wxl882001

    了解一下

    0

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    2018-07-13 yuandd
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