Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
J Virol. 2013 Jun;87(11):6201-10. doi: 10.1128/JVI.00113-13. Epub 2013 Mar 27.
During mouse cytomegalovirus (MCMV) infection, the first wave of type I interferon (IFN-I) production peaks at ≈ 8 h. This IFN-I emanates from splenic stromal cells located in the marginal zone (MZ) and requires B cells that express lymphotoxin. The amount of IFN-I produced at these initial times is at least equivalent in magnitude to that produced later by dendritic cells (≈ 36 to 48 h), but the relative roles of these two IFN-I sources in regulating MCMV defense remain unclear. Here we show that IFN-I produced by MZ stromal cells dramatically restricts the first measurable burst of viral production, which occurs at ≈ 32 h. This primary innate control by IFN-I is partially mediated through the activation of natural killer (NK) cells, which produce gamma interferon in an IFN-I-dependent fashion, and is independent of Ly49H. Strikingly, MCMV production in the spleens of immunocompetent mice never increases at times after 32 h. These results highlight the critical importance of lymphoid-tissue stromal cells in orchestrating the earliest phase of innate defense to MCMV infection, capping replication levels, and blocking spread until infection is ultimately controlled.
在小鼠巨细胞病毒（MCMV）感染期间，第一波 I 型干扰素（IFN-I）的产生在约 8 小时达到峰值。这种 IFN-I 源自位于边缘区（MZ）的脾脏基质细胞，需要表达淋巴毒素的 B 细胞。在这些初始时间产生的 IFN-I 的量至少与树突状细胞（约 36 至 48 小时）后来产生的 IFN-I 相当，但这两种 IFN-I 来源在调节 MCMV 防御中的相对作用仍不清楚。在这里，我们表明，MZ 基质细胞产生的 IFN-I 显著限制了大约在 32 小时发生的第一个可测量的病毒产生爆发。这种 IFN-I 的原发性先天控制部分是通过自然杀伤（NK）细胞的激活介导的，NK 细胞以 IFN-I 依赖的方式产生γ干扰素，并且独立于 Ly49H。引人注目的是，免疫功能正常的小鼠脾脏中的 MCMV 产生从未在 32 小时后增加。这些结果强调了淋巴组织基质细胞在协调对 MCMV 感染的最初先天防御阶段中的关键重要性，限制了复制水平，并阻止了传播，直到感染最终得到控制。
