Monocyte Recruitment to the Dermis and Differentiation to Dendritic Cells Increases the Targets for Dengue Virus Replication

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The skin and its immune cells are an important barrier against invading pathogens. Dengue is a major public health problem worldwide, with no specific therapeutic or vaccine available. Aedes mosquitoes transmit dengue virus (DENV) to humans via the skin when taking a blood meal. Previous studies have examined DENV infection only in the epidermis, the uppermost layer of the skin, but no information existed about DENV infection in the dermis, the layer below that contains blood vessels. We established a model of DENV infection in the skin of mouse ears, as biopsies from naturally-infected human skin are unavailable. The normal dermis contains classical dendritic cells (DCs) and macrophages, which we found to be the initial targets of DENV infection. Monocytes that circulate in the blood were then recruited to the dermis and differentiated to monocyte-derived DCs, an inflammatory DC subset. These newly-recruited monocytes and monocyte-derived DCs became DENV-infected in a second wave and then were the major targets for DENV replication. Our study identifies how DENV exploits the immune response by infecting cells that are recruited to the skin as part of antiviral defense. These results should help future research to develop new strategies for vaccination and therapeutics against dengue.

Vyšlo v časopise: Monocyte Recruitment to the Dermis and Differentiation to Dendritic Cells Increases the Targets for Dengue Virus Replication. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004541
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004541

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