Involvement of caspase-4 in IL-1 beta production and pyroptosis in human macrophages during dengue virus infection |
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Authors: | Ka Tik Cheung Daniel Man-yuen Sze Kwok Hung Chan Polly Hang-mei Leung |
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Affiliation: | 1. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China;2. School of Health and Biomedical Sciences, RMIT University, Australia;3. Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, China |
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Abstract: | Caspase-4 physically interacts with caspase-1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin (IL)-1β. However, the function of caspase-4 in dengue virus infection is not yet fully understood. We examined the function of caspase-4 in IL-1β production and pyroptosis during dengue virus serotype-2 (DENV-2) infection in human macrophages. In this study, DENV-2 infection increased IL-1β protein level with activated caspase-4 activity. Using primary macrophages, we observed that caspase-4 induces activation of caspase-1 and secretion of IL-1β in response to DENV-2 infection, without the need for secondary signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by capsase-4 could represent a unique mechanism. Our data suggest that caspase-4 is upstream of caspase-1 in the pathway that regulates pyroptosis and IL-1β synthesis in macrophages during DENV-2 infection. |
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Keywords: | DF dengue fever DHF dengue hemorrhagic fever IL interleukin TNFα tumor necrosis factor-alpha rNTP ribonucleotide-phosphates LRR leucine-rich repeat LDH lactate dehydrogenase ASC adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain NLR Nod-like receptor family PAMPs pathogen-associated molecular patterns Pyroptosis Dengue virus Caspase-4 Interleukin-1β Inflammasome |
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