title: Dendritic cell subtypes from lymph nodes and blood show contrasted gene expression programs upon Bluetongue virus infection.
abstract: Human and animal hemorrhagic viruses initially target dendritic cells (DCs). It has been proposed, but not documented, that both plasmacytoid DCs (pDCs) and conventional DCs (cDCs) may participate in the cytokine storm encountered in these infections. In order to evaluate the contribution of DCs in hemorrhagic virus pathogenesis, we performed a genome-wide expression analysis during infection by Bluetongue virus (BTV), a double-stranded RNA virus that induces hemorrhagic fever in sheep and initially infects cDCs. Both pDCs and cDCs accumulated in regional lymph nodes and spleen during BTV infection. The gene response profiles were performed at the onset of the disease and markedly differed with the DC subtypes and their lymphoid organ location. An integrative knowledge-based analysis revealed that blood pDCs displayed a gene signature related to activation of systemic inflammation and permeability of vasculature. In contrast, the gene profile of pDCs and cDCs in lymph nodes was oriented to inhibition of inflammation, whereas spleen cDCs did not show a clear functional orientation. These analyses indicate that tissue location and DC subtype affect the functional gene expression program induced by BTV and suggest the involvement of blood pDCs in the inflammation and plasma leakage/hemorrhage during BTV infection in the real natural host of the virus. These findings open the avenue to target DCs for therapeutic interventions in viral hemorrhagic diseases.
authors.affiliation: Virologie et Immunologie Moléculaires, UR892 INRA, Domaine de Vilvert, Jouy-en-Josas, France.
authors.forename: Suzana
authors.initials: S
authors.lastname: Ruscanu
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.forename: Céline
authors.initials: C
authors.lastname: Urien
authors.forename: Mickael
authors.initials: M
authors.lastname: Bourge
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lecardonnel
authors.forename: Marco
authors.initials: M
authors.lastname: Moroldo
authors.forename: Benoit
authors.initials: B
authors.lastname: Loup
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.forename: Jamila
authors.initials: J
authors.lastname: Elhmouzi-Younes
authors.forename: Claudia
authors.initials: C
authors.lastname: Bevilacqua
authors.forename: Jayne
authors.initials: J
authors.lastname: Hope
authors.forename: Damien
authors.initials: D
authors.lastname: Vitour
authors.forename: Stéphan
authors.initials: S
authors.lastname: Zientara
authors.forename: Gilles
authors.initials: G
authors.lastname: Meyer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schwartz-Cornil
mesh_terms: D000818:Animals; D001769:Blood / Q000276:immunology*; D001819:Bluetongue / Q000276:immunology*; D001820:Bluetongue virus / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D012756:Sheep