Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal f
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Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration Jose´ Bustos-Arriaga1,2 • Neida K. Mita-Mendoza3 • Moises Lopez-Gonzalez1 • Julio Garcı´a-Cordero1 • Francisco J. Jua´rez-Delgado4 • Gregory D. Gromowski2 Rene´ A. Me´ndez-Cruz5 • Rick M. Fairhurst3 • Stephen S. Whitehead2 • Leticia Cedillo-Barro´n1
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Ó Springer Science+Business Media New York 2015
Abstract When dengue virus (DENV)-infected mosquitoes use their proboscis to probe into human skin during blood feeding, both saliva and virus are released. During this process, cells from the epidermis and dermis layers of the skin, along with small blood vessels, may get exposed to or infected with DENV. In these microenvironments of the skin, the presence of DENV initiates a complex interplay among the DENV-infected and non-infected neighboring cells at the initial bite site. Previous studies suggested that DENV-infected human dermal fibroblasts (HDFs) participate in the immune response against DENV by secreting soluble mediators of innate immunity. In the present study, we investigated whether DENV-infected HDFs activate human dermal microvascular endothelial cells (HDMECs) in co-cultures. Our results suggest that cocultures of DENV-infected HDFs and HDMECs elicit soluble mediators that are sufficient to reduce viral replication, activate HDMECs, and induce leukocyte migration through HDMEC monolayers. These effects were partly & Leticia Cedillo-Barro´n [email protected] 1
Departmento de Biomedicina Molecular, Centro de Investigacio´n y de Estudios Avanzados, Instituto Polite´cnico Nacional, Mexico, Distrito Federal, Mexico
2
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
3
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
4
Departamento de Cirugia, Hospital General Ticoma´n S.S., Mexico, Distrito Federal, Mexico
5
Laboratorio de Inmunologı´a UMF, FES Iztacala, Universidad Auto´noma de Me´xico, Mexico, Distrito Federal, Mexico
dependent on HDF donor and DENV serotype, which may provide novel insights into the natural variation in host susceptibility to DENV disease. Keywords Dengue Innate immunity Skin Cellular crosstalk Fibroblast and endothelial cells
Introduction Dengue virus (DENV) is transmitted to humans by female Aedes aegypti and Aedes albopictus mosquitoes, which inoculate virus into the dermis and epidermis while taking a blood meal. In this anatomical region of the skin, the virus encounters skin-resident immune cells such as dendritic cells (DCs), a/b and c/d T cells, natural killer (NK) cells, mast cells, and macrophages. However, non-hematopoietic cells such as microvasculature endothelial cells, fibroblasts, keratinocytes, and melanocytes are also abundant in the skin [1, 2]. While some of th
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