Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France.
Eur J Immunol. 2012 Jul;42(7):1822-32. doi: 10.1002/eji.201142099.
Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Arenaviruses. LASV causes hemorrhagic fever, whereas MOPV is not pathogenic. Both viruses display tropism for APCs such as DCs and macrophages. During viral infections, NK cells are involved in the clearance of infected cells and promote optimal immune responses by interacting with APCs. We used an in vitro model of human NK and APC coculture to study the role of NK cells and to characterize their interactions with APCs during LASV and MOPV infections. As expected, NK cells alone were neither infected nor activated by LASV and MOPV, and infected DCs did not activate NK cells. By contrast, LASV- and MOPV-infected macrophages activated NK cells, as shown by the upregulation of CD69, NKp30, and NKp44, the downregulation of CXCR3, and an increase in NK-cell proliferation. NK cells acquired enhanced cytotoxicity, as illustrated by the increase in granzyme B (GrzB) expression and killing of K562 targets, but did not produce IFN-γ. Contact between NK cells and infected macrophages and type I IFNs were essential for activation; however, NK cells could not kill infected cells and control infection. Overall, these findings show that MOPV- as well as pathogenic LASV-infected macrophages mediate NK-cell activation.
拉萨病毒（LASV）和莫比奥病毒（MOPV）是密切相关的沙粒病毒。LASV 引起出血热，而 MOPV 则没有致病性。这两种病毒都对 APC 如树突状细胞和巨噬细胞具有趋化性。在病毒感染期间，NK 细胞通过与 APC 相互作用参与清除受感染的细胞并促进最佳的免疫反应。我们使用人类 NK 和 APC 共培养的体外模型来研究 NK 细胞的作用，并在 LASV 和 MOPV 感染期间表征它们与 APC 的相互作用。如预期的那样，NK 细胞本身既不受 LASV 和 MOPV 的感染也不会被其激活，并且受感染的 DC 也不会激活 NK 细胞。相比之下，LASV 和 MOPV 感染的巨噬细胞激活了 NK 细胞，这表现为 CD69、NKp30 和 NKp44 的上调、CXCR3 的下调以及 NK 细胞增殖的增加。NK 细胞获得了增强的细胞毒性，如 GrzB 表达的增加和对 K562 靶标的杀伤，但不产生 IFN-γ。NK 细胞与受感染的巨噬细胞之间的接触和 I 型 IFNs 对于激活是必需的；然而，NK 细胞不能杀死受感染的细胞并控制感染。总的来说，这些发现表明，MOPV 以及致病性 LASV 感染的巨噬细胞介导了 NK 细胞的激活。
