Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression
Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression
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DOI：
10.1073/pnas.1610012113
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发表时间：
2016-10-11
影响因子：
11.1
通讯作者：
Palmarini, Massimo
中科院分区：
文献类型：
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作者：
Melzi, Eleonora;Caporale, Marco;Palmarini, Massimo
虫媒病毒引起的急性疾病日益影响全球健康。我们使用蓝舌病病毒（BTV）和它的天然绵羊宿主来揭示一种以前没有被虫媒病毒用来操纵宿主免疫力的机制。我们的研究表明，BTV，类似于通过皮肤递送的其他抗原，通过淋巴迅速转运到外周淋巴结。在这里，BTV感染并破坏滤泡树突状细胞，阻碍生发中心的B细胞分裂，导致高亲和力和病毒中和抗体的延迟产生。此外，在BTV感染的动物中，对第二抗原的体液免疫应答也受到阻碍。因此，虫媒病毒可以通过诱导急性免疫抑制来逃避宿主的抗病毒反应。虽然是短暂的，但这种免疫抑制发生在感染的关键早期阶段，此时延迟的宿主体液免疫应答可能影响病毒的全身传播和疾病的临床结局。
Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease.