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INTERPLAY BETWEEN KERATINOCYTES AND MYELOID CELLS DRIVES DENGUE VIRUS SPREAD IN HUMAN SKIN
Duangkhae, Parichat et al. | Date Issued: 2018
Author
Duangkhae, Parichat
Erdos, Geza
Ryman, Kate D.
Watkins, Simon C.
Falo, Louis D.
Marques, Ernesto T. A.
Barratt-Boyes, Simon M.
Affilliation
University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, USA / University of Pittsburgh. Graduate School of Public Health. Department of Infectious Diseases and Microbiology. Pittsburgh, PA, USA.
University of Pittsburgh. School of Medicine. Department of Dermatology. Pittsburgh, PA, USA.
University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, USA / University of Pittsburgh. School of Medicine. Department of Microbiology and Molecular Genetics. Pittsburgh, PA, USA.
University of Pittsburgh. School of Medicine. Center for Biologic Imaging. Pittsburgh, PA, USA / University of Pittsburgh. School of Medicine. Department of Cell Biology. Pittsburgh, PA, USA / University of Pittsburgh. School of Medicine. Department of Immunology. Pittsburgh, PA, USA.
University of Pittsburgh. School of Medicine. Department of Dermatology. Pittsburgh, PA, USA / University of Pittsburgh. School of Medicine. Department of Immunology. Pittsburgh, PA, USA.
University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, USA / University of Pittsburgh. Graduate School of Public Health. Department of Infectious Diseases and Microbiology. Pittsburgh, PA, USA / Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.
University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, USA / University of Pittsburgh. Graduate School of Public Health. Department of Infectious Diseases and Microbiology. Pittsburgh, PA, USA / University of Pittsburgh. School of Medicine. Department of Immunology. Pittsburgh, PA, USA.
Abstract
The skin is the site of dengue virus (DENV) transmission following the bite of an infected mosquito, but the contribution of individual cell types within skin to infection is unknown. We studied the dynamics of DENV infection in human skin explants using quantitative in situ imaging. DENV replicated primarily in the epidermis and induced a transient IFN-α response. DENV infected a wide range of cells, including Langerhans cells, macrophages, dermal dendritic cells, mast cells, fibroblasts, and lymphatic endothelium, but keratinocytes were the earliest targets of infection and made up 60% of infected cells over time. Virus inoculation led to recruitment and infection of Langerhans cells, macrophages, and dermal dendritic cells, and these cells emigrated from skin in increased numbers as a result of infection. DENV induced expression of proinflammatory cytokines and chemokines by infected keratinocytes. Blocking keratinocyte-derived IL-1β alone reduced infection of Langerhans cells, macrophages, and dermal dendritic cells by 75-90% and reduced the overall number of infected cells in dermis by 65%. These data show that the innate response of infected keratinocytes attracts virus-permissive myeloid cells that inadvertently spread DENV infection. Our findings highlight a role for keratinocytes and their interplay with myeloid cells in dengue.
Keywords
Interferon-alfa
Interleucina-1
Queratinócitos
Células Mielóides
 
DeCS
Comunicação Celular
Movimento celular
Quimiocina CCL20 / fisiologia
Vírus da Dengue / fisiologia
Humanos
Interferon-alfa / biossíntese
Interleucina-1 / fisiologia
Queratinócitos / virologia
Células Mielóides / virologia
Pele / virologia
Replicação de Vírus
 
Citation
DUANGKHAE, P. et al. Interplay between Keratinocytes and Myeloid Cells Drives Dengue Virus Spread in Human Skin. The Journal of Investigative Dermatology, v. 138, n. 3, p. 618–626, 2018.
DOI
10.1016/j.jid.2017.10.018
ISSN
1523-1747