Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
Cell Host Microbe. 2014 Mar 12;15(3):351-62. doi: 10.1016/j.chom.2014.02.002.
Peripheral blood myelomonocytic cells are important for cytomegalovirus dissemination to distal organs such as salivary glands where persistent replication and shedding dictates transmission patterns. We find that this process is markedly enhanced by the murine cytomegalovirus (MCMV)-encoded CC chemokine, MCK2, which promotes recruitment of CX3CR1(hi) patrolling monocytes to initial infection sites in the mouse. There, these cells become infected and traffic via the bloodstream to distal sites. In contrast, inflammatory monocytes, the other major myelomonocytic subset, remain virus negative. CX3CR1 deficiency prevents patrolling monocyte migration on the vascular endothelium and interrupts MCMV dissemination to the salivary glands independent of antiviral NK and T cell immune control. In this manner, CX3CR1(hi) patrolling monocytes serve as immune-privileged vehicles to transport MCMV via the bloodstream to distal organs. MCMV commandeers patrolling monocytes to mediate systemic infection and seed a persistent reservoir essential for horizontal transmission.
外周血髓样细胞对于巨细胞病毒向唾液腺等远端器官的扩散至关重要，在这些器官中，持续的复制和脱落决定了传播模式。我们发现，这种过程明显受到了鼠巨细胞病毒（MCMV）编码的 CC 趋化因子 MCK2 的促进，MCK2 促进了 CX3CR1（高）巡弋单核细胞向小鼠初始感染部位的募集。在那里，这些细胞被感染，并通过血液传播到远端部位。相比之下，炎症单核细胞是另一种主要的髓样细胞亚群，仍然是病毒阴性的。CX3CR1 缺陷会阻止巡弋单核细胞在血管内皮上的迁移，并阻断 MCMV 向唾液腺的传播，而与抗病毒 NK 和 T 细胞免疫控制无关。通过这种方式，CX3CR1（高）巡弋单核细胞作为免疫特权载体，通过血液将 MCMV 运输到远端器官。MCMV 利用巡弋单核细胞来介导全身性感染，并为水平传播建立必要的持久性储存库。
