title: Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration.
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 co-cultures 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 dependent on HDF donor and DENV serotype, which may provide novel insights into the natural variation in host susceptibility to DENV disease.
authors.affiliation: Departmento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico, Distrito Federal, Mexico.|Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: José
authors.initials: J
authors.lastname: Bustos-Arriaga
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: Neida K
authors.initials: NK
authors.lastname: Mita-Mendoza
authors.affiliation: Departmento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico, Distrito Federal, Mexico.
authors.forename: Moises
authors.initials: M
authors.lastname: Lopez-Gonzalez
authors.affiliation: Departmento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico, Distrito Federal, Mexico.
authors.forename: Julio
authors.initials: J
authors.lastname: García-Cordero
authors.affiliation: Departamento de Cirugia, Hospital General Ticomán S.S., Mexico, Distrito Federal, Mexico.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Juárez-Delgado
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gromowski
authors.affiliation: Laboratorio de Inmunología UMF, FES Iztacala, Universidad Autónoma de México, Mexico, Distrito Federal, Mexico.
authors.forename: René A
authors.initials: RA
authors.lastname: Méndez-Cruz
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Whitehead
authors.affiliation: Departmento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico, Distrito Federal, Mexico. lcedillo@cinvestav.mx.
authors.forename: Leticia
authors.initials: L
authors.lastname: Cedillo-Barrón
mesh_terms: D000328:Adult; D015415:Biomarkers; D002450:Cell Communication; D002478:Cells, Cultured; D002675:Child, Preschool; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003715:Dengue / Q000097:blood / Q000378:metabolism / Q000821:virology; D003716:Dengue Virus / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000821:virology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D012867:Skin / Q000166:cytology / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration; D014779:Virus Replication
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins
keywords: Cellular crosstalk; Dengue; Fibroblast and endothelial cells; Innate immunity; Skin