Ekchariyawat Peeraya, Hamel Rodolphe, Bernard Eric, Wichit Sineewanlaya, Surasombatpattana Pornapat, Talignani Loïc, Thomas Frédéric, Choumet Valérie, Yssel Hans, Desprès Philippe, Briant Laurence, Missé Dorothée
Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, Montpellier, France.
Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, CNRS-UMR 5236/UM1/UM2, Montpellier, France.
Infect Genet Evol. 2015 Jun;32:401-8. doi: 10.1016/j.meegid.2015.03.025. Epub 2015 Apr 4.
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.
虫媒病毒对人类构成了新出现的威胁。它们通过受感染节肢动物的叮咬传播给脊椎动物。病毒通过皮肤穿刺并在该器官中沉积从而开始早期传播给脊椎动物。然而，叮咬部位发生的情况在很大程度上仍不为人知。在此，我们报告称，基孔肯雅病毒（CHIKV）和西尼罗河病毒（WNV）尽管属于不同的病毒科，但在原代人皮肤成纤维细胞中引发了共同的抗病毒特征，证明干扰素信号通路上调并导致IFN-β、白细胞介素和趋化因子表达增加。值得注意的是，CHIKV和WNV增强IL-1β表达并诱导半胱天冬酶-1成熟，表明这些病原体能够在驻留皮肤细胞中引发炎性小体程序的激活。CHIKV和WNV还诱导皮肤成纤维细胞中炎性小体传感器AIM2的表达，而用小干扰RNA（siRNA）抑制半胱天冬酶-1和AIM2会干扰这些细胞中CHIKV和WNV诱导的IL-1β产生。最后，发现通过半胱天冬酶-1沉默抑制炎性小体可增强CHIKV在皮肤成纤维细胞中的复制。总之，这些结果表明，在感染虫媒病毒后的早期阶段，皮肤通过激活炎性小体促成促炎和抗病毒微环境。
