Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus
Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus
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DOI：
10.1038/ni.2169
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发表时间：
2012-01-01
影响因子：
30.5
通讯作者：
Lang, Karl S.
中科院分区：
文献类型：
--
作者：
Honke, Nadine;Shaabani, Namir;Lang, Karl S.
先天免疫系统通过I型干扰素限制病毒复制，并诱导病毒抗原呈递给适应性免疫反应的细胞。利用感染水泡性口炎病毒的小鼠，我们分析了先天免疫系统如何抑制病毒的繁殖，但仍然允许将抗原呈递给细胞的适应性免疫反应。我们发现，编码抑制蛋白Usp18的基因在嗜金属巨噬细胞中的表达导致I型干扰素反应性降低，从而允许病毒的局部限制复制。这对于诱导适应性抗病毒免疫反应至关重要，因此对于预防感染的致命后果也是至关重要的。总之，我们发现在边缘区巨噬细胞中加强病毒复制是一种免疫机制，确保产生足够的抗原来有效激活获得性免疫反应。
The innate immune system limits viral replication via type I interferon and also induces the presentation of viral antigens to cells of the adaptive immune response. Using infection of mice with vesicular stomatitis virus, we analyzed how the innate immune system inhibits viral propagation but still allows the presentation of antigen to cells of the adaptive immune response. We found that expression of the gene encoding the inhibitory protein Usp18 in metallophilic macrophages led to lower type I interferon responsiveness, thereby allowing locally restricted replication of virus. This was essential for the induction of adaptive antiviral immune responses and, therefore, for preventing the fatal outcome of infection. In conclusion, we found that enforced viral replication in marginal zone macrophages was an immunological mechanism that ensured the production of sufficient antigen for effective activation of the adaptive immune response.