Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus
Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus
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DOI：
10.1016/j.chom.2007.12.008
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发表时间：
2008-02-01
影响因子：
30.3
通讯作者：
Benedict, Chris A.
中科院分区：
文献类型：
--
作者：
Schneider, Kirsten;Loewendorf, Andrea;Benedict, Chris A.
Toll样受体（TLR）依赖性途径控制IFN α β的产生，IFN α β是包括小鼠巨细胞病毒（MCMV）在内的病毒先天免疫控制中的关键细胞因子。光毒素（LT）α β-LT β受体信号传导途径也是防御MCMV的关键，并被认为有助于IFN β应答。我们发现，MCMV感染后，小鼠缺乏光毒素（LT）α β信号不能安装的双相IFN α β反应的初始部分，但显示正常水平的IFN α β在感染的持续阶段。值得注意的是，LT α β依赖性IFN α β应答不依赖于TLR信号传导。表达LT β的B细胞而非T细胞对于促进初始IFN α β应答是必需的。LT β R的表达是脾基质细胞产生IFN α β转化为MCMV所必需的，并依赖于NF-κ B诱导激酶（NIK）。这些结果揭示了TLR-非依赖性的先天宿主防御策略，其由通过LT α β细胞因子系统与基质细胞通信的B细胞指导。
Toll-like receptor (TLR)-dependent pathways control the production of IFN alpha beta, a key cytokine in innate immune control of viruses including mouse cytomegalovirus; (MCMV). The lymphotoxin (LT) alpha beta-LT beta receptor signaling pathway is also critical for defense against MCMV and thought to aid in the IFN beta response. We find that upon MCMV infection, mice deficient for lymphotoxin (LT)alpha beta signaling cannot mount the initial part of a biphasic IFN alpha beta response, but show normal levels of IFN alpha beta during the sustained phase of infection. Significantly, the LT alpha beta-dependent, IFN alpha beta response is independent of TLR signaling. B, but not T, cells expressing LT beta are essential for promoting the initial IFN alpha beta response. LT beta R expression is required strictly in splenic stromal cells for initial IFN alpha beta production to MCMV and is dependent upon the NF-kappa B-inducing kinase (NIK). These results reveal a TLR-independent innate host defense strategy directed by B cells in communication with stromal cells via the LT alpha beta cytokine system.