Ly49h-deficient C57BL/6 mice: a new mouse cytomegalovirus-susceptible model remains resistant to unrelated pathogens controlled by the NK gene complex.
Ly49h-deficient C57BL/6 mice: a new mouse cytomegalovirus-susceptible model remains resistant to unrelated pathogens controlled by the NK gene complex.
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DOI：
10.4049/jimmunol.181.9.6394
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发表时间：
2008-11-01
期刊：
影响因子：
--
通讯作者：
Vidal SM
中科院分区：
文献类型：
--
作者：
Fodil-Cornu N;Lee SH;Belanger S;Makrigiannis AP;Biron CA;Buller RM;Vidal SM
Cmv1是在C57BL/6小鼠中发现的第一个小鼠巨细胞病毒(MCMV)抗性位点。它编码Ly49H，一种NK细胞激活受体，特异性识别MCMV感染细胞表面的M157病毒蛋白。为了分析Ly49h基因在宿主-病原体相互作用中的作用，我们产生了缺失Ly49h区域的C57BL/6小鼠。我们发现，在MCMV感染36h后，Ly49h的缺失导致了病毒在脾内的高复制，并显著增加了血清和脾中促炎症细胞因子的产生。在随后的时间点上，我们观察到巨细胞病毒诱导了B6.Ly49h−/−小鼠CD8+T细胞的急剧丧失，这可能反映了脾的严重组织学变化。总体而言，我们的结果表明，Ly49H+NK细胞含有系统性产生的细胞因子，这些细胞因子可能参与了MCMV诱导的病理过程，并在维持正常的脾细胞微结构方面发挥了核心作用。最后，我们测试了B6.Ly49h−/−小鼠对大利什曼原虫和外感利什曼原虫病毒复制的控制能力。对这些病原体的抗性已被定位在NK基因复合体中。我们发现Ly49H+NK细胞的缺乏与对主要乳杆菌的抵抗力改变无关。相反，缺乏Ly49H+NK细胞似乎对C57BL/6小鼠的皮肤病感染提供了额外的保护，这表明Ly49H可能识别具有有害影响的皮肤病感染细胞。综上所述，这些结果证实了Ly49H受体在MCMV感染过程中的关键作用，并为进一步研究宿主与病原体的相互作用开辟了道路。
Cmv1 was the first mouse cytomegalovirus (MCMV) resistance locus identified in C57BL/6 mice. It encodes Ly49H, a NK cell-activating receptor that specifically recognizes the m157 viral protein at the surface of MCMV-infected cells. To dissect the effect of the Ly49h gene in host-pathogen interactions, we generated C57BL/6 mice lacking the Ly49h region. We found that 36 h after MCMV infection, the lack of Ly49h resulted in high viral replication in the spleen and dramatically enhanced proinflammatory cytokine production in the serum and spleen. At later points in time, we observed that MCMV induced a drastic loss in CD8+ T cells in B6.Ly49h−/− mice, probably reflecting severe histological changes in the spleen. Overall, our results indicate that Ly49H+ NK cells contain a systemic production of cytokines that may contribute to the MCMV-induced pathology and play a central role in maintaining normal spleen cell microarchitecture. Finally, we tested the ability of B6.Ly49h−/− mice to control replication of Leishmania major and ectromelia virus. Resistance to these pathogens has been previously mapped within the NK gene complex. We found that the lack of Ly49H+ NK cells is not associated with an altered resistance to L. major. In contrast, absence of Ly49H+ NK cells seems to afford additional protection against ectromelia infection in C57BL/6 mice, suggesting that Ly49H may recognize ectromelia-infected cells with detrimental effects. Taken together, these results confirm the pivotal role of the Ly49H receptor during MCMV infection and open the way for further investigations in host-pathogen interactions.
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