Natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liver

Natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liver
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DOI:
10.1128/jvi.79.1.661-667.2005
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发表时间:
2005-01-01
影响因子:
5.4
通讯作者:
Virgin, HW
Virgin, HW
中科院分区:
医学2区
文献类型:
--
作者:
Loh, J;Chu, DT;Virgin, HW

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自然杀伤(NK)细胞对于鼠巨细胞病毒(MCMV)感染的急性期的先天性调节是关键的,并且已报道以器官特异性方式利用穿孔素(Pfp)和γ干扰素(IFN-γ)依赖性效应器机制来调节脾和肝中的MCMV感染。在这项研究中,我们进一步研究了NK细胞,Pfp和IFN-γ在MCMV感染的先天免疫中的作用。与最近描述的NK细胞缺陷(NKD)小鼠,我们证实了以前的研究结果,NK细胞,而不是NKT细胞,需要控制急性期的MCMV感染的脾和肝细胞。有趣的是,我们发现Pfp和IFN-γ对于调节脾脏和肝脏中MCMV复制都很重要。此外,NK细胞可以以Pfp非依赖性方式调节Pfp(-/-)小鼠脾脏和肝脏中的MCMV感染,并且可以使用IFN-γ非依赖性机制来控制IFN-γ(-/-)小鼠中的MCMV感染。因此,与以前的报道相反,NK细胞利用Pfp和IFN-γ来控制脾和肝中的MCMV感染。
Natural killer (NK) cells are critical for innate regulation of the acute phase of murine cytomegalovirus (MCMV) infection and have been reported to utilize perforin (Pfp)- and gamma interferon (IFN-gamma)-dependent effector mechanisms in an organ-specific manner to regulate MCMV infection in the spleen and liver. In this study, we further examined the roles of NK cells, Pfp, and IFN-gamma in innate immunity to MCMV infection. With the recently described NK cell-deficient (NKD) mouse, we confirmed previous findings that NK cells, but not NKT cells, are required for control of the acute phase of MCMV infection in spleen and liver cells. Interestingly, we found that Pfp and IFN-gamma are each important for regulating MCMV replication in both the spleen and the liver. Moreover, NK cells can regulate MCMV infection in the spleens and livers of Pfp(-/-) mice in a Pfp-independent manner and can use an IFN-gamma-independent mechanism to control MCMV infection in IFN-gamma(-/-) mice. Thus, contrary to previous reports, NK cells utilize both Pfp and IFN-gamma to control MCMV infection in the spleen and liver.