Loss of Mandibular Lymph Node Integrity Is Associated with an Increase in Sensitivity to HSV-1 Infection in CD118-Deficient Mice
Loss of Mandibular Lymph Node Integrity Is Associated with an Increase in Sensitivity to HSV-1 Infection in CD118-Deficient Mice
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DOI：
10.4049/jimmunol.0803878
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发表时间：
2009-03-15
影响因子：
4.4
通讯作者：
Carr, Daniel J. J.
中科院分区：
文献类型：
--
作者：
Conrady, Christopher D.;Thapa, Manoj;Carr, Daniel J. J.
I型干扰素是一种有效的抗病毒细胞因子，有助于适应性免疫反应的发展。为了在传染病模型中确定I型干扰素在这一过程中的作用，将I型干扰素受体(CD118(-/-))缺陷的小鼠眼部感染HSV-1，并在感染后的神经系统和淋巴结处观察病毒和宿主免疫反应。CD118(-/-)小鼠三叉神经节和脑干中病毒滴度升高，病毒迅速扩散至引流淋巴结。CD118(-/-)小鼠感染后T细胞和浆细胞样树突状细胞在脑干中的浸润减少，这与CXCL10的表达减少有关，但与CXCL9的表达无关。相比之下，CD118(-/-)小鼠脑干中CXCL1和CCL2水平上调，与F4/80(+)巨噬细胞的增加有关。感染后第5天，引流淋巴结中T细胞、NK细胞和浆细胞样树突状细胞数量显著减少，与凋亡/坏死性T细胞增多和明显缺乏HSV特异性CD8(+)T细胞有关。在感染时将HSV特异性TCR转基因CD8(+)T细胞过继转移到CD118(-/-)小鼠体内，适度降低了神经系统中的病毒滴度，这表明除了产生HSV特异性CD8(+)T细胞外，其他I型干扰素激活的途径也有助于控制急性感染。免疫学杂志，2009,182：3678-3687。
Type I IFNs are potent antiviral cytokines that contribute to the development of the adaptive immune response. To determine the role of type I IFNs in this process in an infectious disease model, mice deficient in the type I IFN receptor (CD118(-/-)) were ocularly infected with HSV-1 and surveyed at times post infection in the nervous system and lymph node for virus and the host immune response. Virus titers were elevated in the trigeminal ganglia and brain stem with virus disseminating rapidly to the draining lymph node of CD118(-/-) mice. T cell and plasmacytoid dendritic cell infiltration into the brain stem was reduced in CD118(-/-) mice following infection, which correlated with a reduction in CXCL10 but not CXCL9 expression. In contrast, CXCL1 and CCL2 levels were up-regulated in the brainstem of CD118(-/-) mice associated with an increase in F4/80(+) macrophages. By day 5 post infection, there was a significant loss in T, NK, and plasmacytoid dendritic cell numbers in the draining lymph nodes associated with an increase in apoptotic/necrotic T cells and an appreciable lack of HSV-specific CD8(+) T cells. The adoptive transfer of HSV-specific TCR transgenic CD8(+) T cells into CD118(-/-) mice at the time of infection modestly reduced viral titers in the nervous system suggesting in addition to the generation of HSV-specific CD8(+) T cells, other type I IFN-activated pathways are instrumental in controlling acute infection. The Journal of Immunology, 2009, 182: 3678-3687.