title: Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts.
abstract: Arboviruses represent an emerging threat to human. They are transmitted to vertebrates by the bite of infected arthropods. Early transmission to vertebrates is initiated by skin puncture and deposition of virus in this organ. However, events at the bite site remain largely unknown. Here, we report that Chikungunya virus (CHIKV) and West Nile virus (WNV), despite belonging to distinct viral families, elicit a common antiviral signature in primary human dermal fibroblasts, attesting for the up regulation of interferon signaling pathways and leading to an increased expression of IFN-β, interleukins and chemokines. Remarkably, CHIKV and WNV enhance IL-1β expression and induce maturation of caspase-1, indicating the capacity of these pathogens to elicit activation of the inflammasome program in resident skin cells. CHIKV and WNV also induce the expression of the inflammasome sensor AIM2 in dermal fibroblasts, whereas inhibition of caspase-1 and AIM2 with siRNA interferes with both CHIKV- and WNV-induced IL-1β production by these cells. Finally, inhibition of the inflammasome via caspase-1 silencing was found to enhance CHIKV replication in dermal fibroblasts. Together, these results indicate that the skin contributes to the pro-inflammatory and anti-viral microenvironment via the activation of the inflammasome in the early stages following infection with arboviruses.
authors.affiliation: Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France.
authors.forename: Peeraya
authors.initials: P
authors.lastname: Ekchariyawat
authors.affiliation: Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Hamel
authors.affiliation: Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, CNRS-UMR 5236/UM1/UM2, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bernard
authors.affiliation: Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France.
authors.forename: Sineewanlaya
authors.initials: S
authors.lastname: Wichit
authors.affiliation: Prince of Songkla University, Pathology Department, Faculty of Medicine, Songkla, Thailand.
authors.forename: Pornapat
authors.initials: P
authors.lastname: Surasombatpattana
authors.affiliation: Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Talignani
authors.affiliation: Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Thomas
authors.affiliation: Unit Environment and Infectious Risks, Institut Pasteur, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Choumet
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses, Inserm, U1135, Sorbonne Universités, UPMC, APHP Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Hans
authors.initials: H
authors.lastname: Yssel
authors.affiliation: Département infections et Epidémiologie, Institut Pasteur, 75724 Paris et UMR PIMIT (I2T team), Université de La Réunion, INSERM U1187, CNRS 9192, IRD 249, GIP-CYROI, 97491 Saint Clotilde, La Réunion, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.affiliation: Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, CNRS-UMR 5236/UM1/UM2, Montpellier, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Briant
authors.affiliation: Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France. Electronic address: dorothee.misse@ird.fr.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Missé
mesh_terms: D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002646:Chikungunya virus / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology*; D020868:Gene Silencing; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D014779:Virus Replication; D014902:West Nile virus / Q000235:genetics / Q000502:physiology
chemical_list: C410167:AIM2 protein, human; D018925:Chemokines; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D016899:Interferon-beta; D007372:Interferons; D020170:Caspase 1
keywords: AIM2; Arbovirus; Caspase 1; Chikungunya virus; Inflammasome; West Nile virus