Essential role for autophagy in the maintenance of immunological memory against influenza infection.

Essential role for autophagy in the maintenance of immunological memory against influenza infection.
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DOI:
10.1038/nm.3521
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发表时间:
2014-05
期刊:
影响因子:
82.9
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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几个世纪以来,疫苗接种一直是最广泛使用的预防病毒感染的策略。然而,免疫记忆对疫苗反应的长期持久性的分子机制仍不清楚。在这里,我们表明,自噬在维持记忆B细胞对流感病毒感染的关键作用。记忆B细胞表现出基础自噬水平升高,同时调节自噬起始或自噬体成熟的基因表达增加。B细胞特异性缺失Atg 7(B/Atg 7 −/−)的小鼠在流感免疫后表现出正常的一抗应答,但在流感病毒攻击时未能产生保护性二抗应答,导致病毒载量高、肺广泛破坏和死亡率增加。我们的研究结果表明,自噬对于病毒特异性记忆B细胞的存活和维持对抗感染所需的保护性抗体反应是必不可少的。
Vaccination has been the most widely used strategy to protect against viral infections for centuries. However, the molecular mechanisms governing the long-term persistence of immunological memory in response to vaccines remain unclear. Here we show that autophagy plays a critical role in the maintenance of memory B cells against influenza virus infection. Memory B cells displayed elevated levels of basal autophagy with increased expression of genes that regulate autophagy initiation or autophagosome maturation. Mice with B cell-specific deletion of Atg7 (B/Atg7−/−) showed normal primary antibody responses after immunization against influenza, but failed to generate protective secondary antibody responses when challenged with influenza viruses, resulting in high viral loads, widespread lung destruction and increased fatality. Our results suggest that autophagy is essential for the survival of virus-specific memory B cells and the maintenance of protective antibody responses required to combat infections.
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