Evidence for differential roles for NKG2D receptor signaling in innate host defense against coronavirus-induced neurological and liver disease.
Evidence for differential roles for NKG2D receptor signaling in innate host defense against coronavirus-induced neurological and liver disease.
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NKG2D 受体信号传导在宿主先天防御冠状病毒引起的神经和肝脏疾病中发挥不同作用的证据。
DOI：
10.1128/jvi.02032-07
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发表时间：
2008
影响因子：
5.4
通讯作者：
Lane,ThomasE
中科院分区：
文献类型：
--
作者：
Walsh,KevinB;Lodoen,MelissaB;Edwards,RobertA;Lanier,LewisL;Lane,ThomasE
用表达T细胞趋化因子CXC趋化因子配体10（CXCL 10）的重组鼠冠状病毒（小鼠肝炎病毒[MHV]）感染SCID小鼠，与用同基因对照病毒（MHV）感染的小鼠相比，导致存活率增加，脑和肝脏内病毒负荷降低，支持CXCL 10在病毒感染后的先天免疫应答中的重要作用。MHV-CXCL 10感染小鼠的保护作用增强与脑内自然杀伤（NK）细胞浸润导致γ干扰素（IFN-γ）产生增加和肝脏病理学减少相关。为了探索与MHV-CXCL 10感染小鼠的疾病保护相关的潜在机制，检查了NK细胞活化受体NKG 2D在宿主防御中的功能贡献。对MHV-CXCL 10感染小鼠给予NKG 2D阻断抗体不会降低存活率、抑制脑中IFN-γ的产生或影响肝脏病理学。然而，NKG 2D中和增加了肝脏内的病毒滴度，表明NKG 2D信号在该器官中具有保护作用。这些数据表明：（i）CXCL 10可增强先天免疫应答，从而防止MHV诱导的神经系统和肝脏疾病;（ii）MHV-CXCL 10感染小鼠脑中NK细胞IFN-γ表达升高与NKG 2D无关;（iii）NKG 2D信号传导可促进MHV感染小鼠肝脏内的抗病毒活性，而不依赖于IFN-γ和肿瘤坏死因子α分泌。
Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.