Vaccinia Virus Infection Inhibits Skin Dendritic Cell Migration to the Draining Lymph Node.
Vaccinia Virus Infection Inhibits Skin Dendritic Cell Migration to the Draining Lymph Node.
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DOI：
10.4049/jimmunol.2000928
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发表时间：
2021-02-15
期刊：
影响因子：
--
通讯作者：
Rothfuchs AG
中科院分区：
文献类型：
--
作者：
Aggio JB;Krmeská V;Ferguson BJ;Wowk PF;Rothfuchs AG
具有复制能力的VACV抑制皮肤DC向引流淋巴结的迁移。VACV抑制效应是皮肤中VACV感染的普遍现象。VACV可以在没有DC转运和致敏CD4+ T细胞的情况下进入淋巴结。关于树突状细胞（DC）对牛痘病毒（VACV）的反应，包括DC向引流淋巴结（dLN）的运输，信息很少。在这项研究中，使用小鼠感染模型，我们研究了皮肤DC迁移对VACV的反应，并将其与结核病疫苗牛分枝杆菌卡介苗（BCG）进行了比较，BCG是另一种通过皮肤接种的减毒活疫苗。与BCG形成鲜明对比的是，皮肤DC没有响应于VACV而重新定位到dLN。用UV灭活的VACV或改良的VACV Ankara感染促进DC向dLN移动，表明干扰皮肤DC迁移需要复制能力的VACV。VACV的这种抑制作用能够减轻皮肤中对BCG二次激发的反应，消融DC迁移，减少BCG转运，并延迟dLN中的CD4+ T细胞引发。与BCG触发的DC迁移相关的炎症介质的表达在病毒注射的皮肤中不存在，这表明其他途径引起DC运动以响应复制缺陷的VACV。尽管DC迁移的顽固抑制，VACV仍然在dLN和致敏的Ag特异性CD4+ T细胞中早期检测到。总之，VACV阻断了皮肤DC从感染部位的动员，同时保留了进入dLN以引发CD4+ T细胞的能力。
Replication-competent VACV inhibits skin DC migration to draining lymph node. The VACV-suppressive effect is a general phenomenon of VACV infection in the skin. VACV can access the lymph node in the absence of DC transport and prime CD4+ T cells. There is a paucity of information on dendritic cell (DC) responses to vaccinia virus (VACV), including the traffic of DCs to the draining lymph node (dLN). In this study, using a mouse model of infection, we studied skin DC migration in response to VACV and compared it with the tuberculosis vaccine Mycobacterium bovis bacille Calmette–Guérin (BCG), another live attenuated vaccine administered via the skin. In stark contrast to BCG, skin DCs did not relocate to the dLN in response to VACV. Infection with UV-inactivated VACV or modified VACV Ankara promoted DC movement to the dLN, indicating that interference with skin DC migration requires replication-competent VACV. This suppressive effect of VACV was capable of mitigating responses to a secondary challenge with BCG in the skin, ablating DC migration, reducing BCG transport, and delaying CD4+ T cell priming in the dLN. Expression of inflammatory mediators associated with BCG-triggered DC migration were absent from virus-injected skin, suggesting that other pathways invoke DC movement in response to replication-deficient VACV. Despite adamant suppression of DC migration, VACV was still detected early in the dLN and primed Ag-specific CD4+ T cells. In summary, VACV blocks skin DC mobilization from the site of infection while retaining the ability to access the dLN to prime CD4+ T cells.
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影响因子：
32.4
作者：
Egen JG;Rothfuchs AG;Feng CG;Horwitz MA;Sher A;Germain RN
通讯作者：
Germain RN
影响因子：
5.4
作者：
Humrich, Jens Y.;Thumann, Peter;Jenne, Lars
通讯作者：
Jenne, Lars
影响因子：
64.5
作者：
ALCAMI, A;SMITH, GL
通讯作者：
SMITH, GL
影响因子：
30.5
作者：
Bedoui, Sammy;Whitney, Paul G.;Heath, William R.
通讯作者：
Heath, William R.
影响因子：
4.4
作者：
Grayson, Mitchell H.;Ramos, Madeleine S.;Holtzman, Michael J.
通讯作者：
Holtzman, Michael J.