title: Dengue virus-infected human monocytes trigger late activation of caspase-1, which mediates pro-inflammatory IL-1β secretion and pyroptosis.
abstract: Dengue virus (DENV) infection affects millions of people annually and has the potential to cause fatal haemorrhagic fever and shock. Although the underlying pathogenesis of severe dengue illness is still unclear, current evidence suggests that severe disease progression has an immunological basis. In this study, we investigated the role of caspase-1 during host-pathogen interactions within DENV-infected human monocytes. Using DENV-infected primary monocytes, we examined caspase-1 at various levels of gene expression and probed for potential immune consequences mediated by caspase-1 such as secretion of pro-inflammatory IL-1β and pyroptotic cell death. We report that DENV-infected monocytes upregulated functional caspase-1 mRNA and pro-caspase-1 activation as a late response to infection. In addition, we found that caspase-1 is responsible for IL-1β secretion and pyroptosis of DENV-infected monocytes. Together, our results show that late caspase-1 activation within DENV-infected monocytes can contribute to pro-inflammatory outcomes that might play a role in dengue immunopathogenesis.
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, MD4, 5 Science Drive 2, National University of Singapore, Singapore 117597.
authors.forename: Ter Yong
authors.initials: TY
authors.lastname: Tan
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, MD4, 5 Science Drive 2, National University of Singapore, Singapore 117597.
authors.forename: Justin Jang Hann
authors.initials: JJH
authors.lastname: Chu
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology / Q000821:virology*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D053583:Interleukin-1beta; D020170:Caspase 1