Vaccinia Virus Infection Inhibits Skin Dendritic Cell Migration to Draining Lymph Node

Despite the success of Vaccinia virus (VACV) against smallpox there remains a paucity of information on Dendritic cell (DC) responses to the virus, especially on the traffic of DCs and VACV to draining LN (dLN). Herein we studied skin DC migration in response to VACV and compared it to 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 dLN in response to VACV. This happened in spite of virus-induced accumulation of several other innate-immune cell populations in the dLN. UV inactivation of VACV or use of the Modified Vaccinia virus Ankara (MVA) strain promoted DC movement to dLN, indicating that the virus actively interferes with skin DC migration. This active immune suppression by VACV was potent enough to ablate the mobilization of skin DCs in response to BCG, and to reduce the transport of BCG to dLN. Expression of inflammatory mediators associated with BCG-triggered DC migration were absent from virus-injected skin, suggesting that other pathways provoke DC movement in response to replication-deficient VACV. Despite viral suppression of DC migration, VACV was detected in dLN much earlier than BCG, indicating a rapid, alternative route of viral traffic to dLN despite marked blockade of skin DC mobilization from the site of infection.