Format

Send to

Choose Destination
Infect Genet Evol. 2015 Jun;32:401-8. doi: 10.1016/j.meegid.2015.03.025. Epub 2015 Apr 4.

Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts.

Author information

1
Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France.
2
Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, CNRS-UMR 5236/UM1/UM2, Montpellier, France.
3
Prince of Songkla University, Pathology Department, Faculty of Medicine, Songkla, Thailand.
4
Unit Environment and Infectious Risks, Institut Pasteur, Paris, France.
5
Centre d'Immunologie et des Maladies Infectieuses, Inserm, U1135, Sorbonne Universités, UPMC, APHP Hôpital Pitié-Salpêtrière, Paris, France.
6
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.
7
Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France. Electronic address: dorothee.misse@ird.fr.

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.

KEYWORDS:

AIM2; Arbovirus; Caspase 1; Chikungunya virus; Inflammasome; West Nile virus

PMID:
25847693
DOI:
10.1016/j.meegid.2015.03.025
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center