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

Juliana Bernardi Aggio,Veronika Krmeská,Brian J Ferguson,Antonio Gigliotti Rothfuchs,Pryscilla Fanini Wowk

doi:10.4049/jimmunol.2000928

Juliana Bernardi Aggio, Veronika Krmeská + Show 3 more

Open Access

https://doi.org/10.4049/jimmunol.2000928

Copy DOI

Abstract

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.

Highlights

Unlike the early reaction to bacille Calmette–Guerin (BCG), we found that vaccinia virus (VACV) actively inhibits skin dendritic cell (DC) migration to the draining lymph node (dLN) but retains the ability to enter the dLN in the absence of DC transport and prime CD4+ T cells therein
To investigate DC migration in response to VACV, we inoculated the virus in the footpad skin of C57BL/6 wild-type mice and used a CFSE fluorochrome-based migration assay to track the movement of skin DCs to the dLN and popliteal LN (pLN) [3, 25]
The absence of CFSE labeling in skin DCs in the dLN of VACV-infected mice was not concurrent with CFSE labeling in other MHC class II (MHC-II)+ cells or even in MHC-II–negative populations, suggesting a generalized absence of cells moving from skin to the dLN in response to the virus (Fig. 1C)

Summary

Introduction

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. Using an infection model in mice and a novel assay to track DC migration in vivo, we have previously identified a role for IL-1R signaling in mobilizing skin DCs to the dLN in response to Mycobacterium bovis bacille Following inoculation of VACV in the skin, infected cells, including DCs and macrophages, can be detected in the dLN within a few hours [9,10,11,12].

Results

Conclusion