Cell-intrinsic Innate Immune Responses against Chikungunya Virus in a Human Ex Vivo Synovial Fibroblast Model

摘要: In recent years, newly and re-emerging arboviruses including Chikungunya virus (CHIKV), have caused growing concern due to expansion of insect vector ranges, mediated by the exponential increase in international travel accelerating climate change. Due absence specific antiviral treatment strategies a protective vaccine, over 2 million CHIKV cases been reported since 2005. Long-term morbidity after infection includes debilitating chronic joint pain, which has associated health, social, individual, economic impact. Here, we analyzed early cell-intrinsic response primary human synovial fibroblasts. This cell type represents potential source polyarthralgia induced infection. Synovial fibroblasts from healthy donors osteoarthritic patients were similarly permissive We observed infection-induced transcriptional profile that consisted upregulation several hundred interferon-stimulated genes, addition transcription factor-encoding genes effector proinflammatory pathways. contrast, IL-6, mediates synovitis stimulating neutrophil macrophage infiltration into joints, was barely secreted CHIKV-infected Finally, interferon I III differed immortalized model lines. fibroblasts, replication impaired IFN-α administered post-infection. summary, serve as bona-fide ex vivo provide valuable platform for studies tissue-associated aspects immunopathogenesis.