Ly6C+ monocytes in the skin promote systemic alphavirus dissemination
Autumn C. Holmes,
Cormac J. Lucas,
Morgan E. Brisse,
Brian C. Ware,
Heather D. Hickman,
Thomas E. Morrison,
Michael S. Diamond
Affiliations
Autumn C. Holmes
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Cormac J. Lucas
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
Morgan E. Brisse
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Microbiology and Immunology, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
Brian C. Ware
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
Heather D. Hickman
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Microbiology and Immunology, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
Thomas E. Morrison
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
Michael S. Diamond
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; Andrew M. and Jane M. Bursky the Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA; Corresponding author
Summary: 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.
