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Publication : Ly6C(+) monocytes in the skin promote systemic alphavirus dissemination.

First Author  Holmes AC Year  2024
Journal  Cell Rep Volume  43
Issue  3 Pages  113876
PubMed ID  38446669 Mgi Jnum  J:346715
Mgi Id  MGI:7618045 Doi  10.1016/j.celrep.2024.113876
Citation  Holmes AC, et al. (2024) Ly6C(+) monocytes in the skin promote systemic alphavirus dissemination. Cell Rep 43(3):113876
abstractText  Alphaviruses are mosquito-transmitted pathogens that induce high levels of viremia, which facilitates dissemination and vector transmission. One prevailing paradigm is that, after skin inoculation, alphavirus-infected resident dendritic cells migrate to the draining lymph node (DLN), facilitating further rounds of infection and dissemination. Here, we assess the contribution of infiltrating myeloid cells to alphavirus spread. We observe two phases of virus transport to the DLN, one that occurs starting at 1 h post infection and precedes viral replication, and a second that requires replication in the skin, enabling transit to the bloodstream. Depletion of Ly6C(+) monocytes reduces local chikungunya (CHIKV) or Ross River virus (RRV) infection in the skin, diminishes the second phase of virus transport to the DLN, and delays spread to distal sites. Our data suggest that infiltrating monocytes facilitate alphavirus infection at the initial infection site, which promotes more rapid spread into circulation.
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