Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
J Virol. 2012 Oct;86(20):11254-65. doi: 10.1128/JVI.00576-12. Epub 2012 Aug 8.
Type I interferons (IFNs), predominantly IFN-α and -β, play critical roles in both innate and adaptive immune responses against viral infections. Interferon regulatory factor 7 (IRF7), a key innate immune molecule in the type I IFN signaling pathway, is essential for the type I IFN response to many viruses, including lymphocytic choriomeningitis virus (LCMV). Here, we show that although IRF7 knockout (KO) mice failed to control the replication of LCMV in the early stages of infection, they were capable of clearing LCMV infection. Despite the lack of type I IFN production, IRF7 KO mice generated normal CD4(+) T cell responses, and the expansion of naïve CD8(+) T cells into primary CD8(+) T cells specific for LCMV GP(33-41) was relatively normal. In contrast, the expansion of the LCMV NP(396)-specific CD8(+) T cells was severely impaired in IRF7 KO mice. We demonstrated that this defective CD8(+) T cell response is due neither to an impaired antigen-presenting system nor to any intrinsic role of IRF7 in CD8(+) T cells. The lack of a type I IFN response in IRF7 KO mice did not affect the formation of memory CD8(+) T cells. Thus, the present study provides new insight into the impact of the innate immune system on viral pathogenesis and demonstrates the critical contribution of innate immunity in controlling virus replication in the early stages of infection, which may shape the quality of CD8(+) T cell responses.
I 型干扰素（IFN），主要包括 IFN-α 和 -β，在抗病毒感染的固有和适应性免疫反应中发挥关键作用。干扰素调节因子 7（IRF7）是 I 型 IFN 信号通路中的关键先天免疫分子，对于许多病毒（包括淋巴细胞性脉络丛脑膜炎病毒[LCMV]）的 I 型 IFN 反应至关重要。在这里，我们表明，尽管 IRF7 敲除（KO）小鼠无法控制 LCMV 在感染早期的复制，但它们能够清除 LCMV 感染。尽管缺乏 I 型 IFN 的产生，IRF7 KO 小鼠仍能产生正常的 CD4(+) T 细胞反应，并且幼稚 CD8(+) T 细胞扩增为针对 LCMV GP(33-41)的初级 CD8(+) T 细胞相对正常。相比之下，IRF7 KO 小鼠中 LCMV NP(396)-特异性 CD8(+) T 细胞的扩增严重受损。我们证明，这种缺陷的 CD8(+) T 细胞反应既不是由于抗原呈递系统受损，也不是由于 IRF7 在 CD8(+) T 细胞中的任何内在作用所致。IRF7 KO 小鼠中缺乏 I 型 IFN 反应并不影响记忆 CD8(+) T 细胞的形成。因此，本研究提供了对固有免疫系统对病毒发病机制的影响的新见解，并证明了固有免疫在控制感染早期病毒复制方面的关键作用，这可能会影响 CD8(+) T 细胞反应的质量。
