Multiple effects of dendritic cell depletion on murine norovirus infection
Multiple effects of dendritic cell depletion on murine norovirus infection
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DOI：
10.1099/vir.0.052134-0
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发表时间：
2013-08-01
影响因子：
3.8
通讯作者：
Wobus, Christiane E.
中科院分区：
文献类型：
--
作者：
Elftman, Michael D.;Gonzalez-Hernandez, Mariam B.;Wobus, Christiane E.
树突状细胞（Dendritic cells，DCs）在体内外均能耐受鼠诺如病毒（murine norovirus，MNV）感染。然而，它们在体内感染过程中的作用还没有很好的定义。为了确定DCs在感染过程中的作用，从CD 11 c-DTR小鼠中耗尽常规DCs并用持续性MNV株感染。在肠道和次级淋巴器官的病毒滴度在感染过程中的早期时间点进行了测定，并在感染过程中的抗MNV抗体反应进行了分析。常规DC的消耗导致肠组织中病毒载量增加，抗体应答的产生受损，并且MNV不能有效地感染淋巴组织。这些数据表明，DC在MNV发病机制中发挥多种作用，包括先天免疫和有效产生针对MNV的适应性免疫应答。以及通过促进MNV向次级淋巴组织的传播。这是第一项研究，以探讨在控制和/或促进诺如病毒感染在体内的DC的作用，并提供了基础，旨在确定机制，DC控制MNV复制和促进病毒传播的进一步研究。
Dendritic cells (DCs) are permissive to murine norovirus (MNV) infection in vitro and in vivo. However, their roles during infection in vivo are not well defined. To determine the role of DCs during infection, conventional DCs were depleted from CD11c-DTR mice and infected with a persistent MNV strain. Viral titres in the intestine and secondary lymphoid organs were determined at early time points during infection, and anti-MNV antibody responses were analysed later during infection. Depletion of conventional DCs resulted in increased viral loads in intestinal tissues, impaired generation of antibody responses, and a failure of MNV to efficiently infect lymphoid tissues. These data suggest that DCs play multiple roles in MNV pathogenesis, in both innate immunity and the efficient generation of adaptive immune responses against MNV., as well as by promoting the dissemination of MNV to secondary lymphoid tissues. This is the first study to probe the roles of DCs in controlling and/or facilitating a norovirus infection in vivo and provides the basis for further studies aimed at defining mechanisms by which DCs control MNV replication and promote viral dissemination.