Ly6C+ monocytes in the skin promote systemic alphavirus dissemination

• Published in: Cell reports (Cambridge) Vol. 43; no. 3; p. 113876
• Main Authors: Holmes, Autumn C., Lucas, Cormac J., Brisse, Morgan E., Ware, Brian C., Hickman, Heather D., Morrison, Thomas E., Diamond, Michael S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2024; Elsevier
• Subjects: alphavirus; Animals; Chikungunya Fever - pathology; Chikungunya virus; CP: Immunology; CP: Microbiology; dissemination; immunity; lymph node; monocytes; Monocytes - pathology; Mosquito Vectors; mouse models; Myeloid Cells; pathogenesis; viremia; Virus Replication; mouse models; CP: Immunology; pathogenesis; monocytes; dissemination; lymph node; CP: Microbiology; alphavirus; immunity; viremia
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113876

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. [Display omitted] •Skin-associated monocytes are required for efficient CHIKV and RRV dissemination•Skin-associated infiltrating monocytes are targets of CHIKV infection•Monocytes promote CHIKV replication in non-hematopoietic cells of the skin•Lymph node monocytes are not permissive to CHIKV infection Holmes et al. demonstrate that infiltrating Ly6Chi monocytes in the skin facilitate dissemination of CHIKV through the lymphatics into circulation. Monocytes in the skin become infected and boost the amount of CHIKV produced by nearby stromal cells, resulting in enhanced virus transit to the draining lymph node and systemic spread.