Involvement of caspase-4 in IL-1 beta production and pyroptosis in human macrophages during dengue virus infection

• Published in: Immunobiology (1979) 2018-04, Vol.223 (4-5), p.356-364
• Main Authors: Cheung, Ka Tik, Sze, Daniel Man-yuen, Chan, Kwok Hung, Leung, Polly Hang-mei
• Format: Article
• Language: English
• Subjects: Caspase 1 - metabolism; Caspase-4; Caspases, Initiator - metabolism; Cells, Cultured; Dengue - immunology; Dengue virus; Dengue Virus - immunology; Humans; Inflammasome; Inflammasomes - metabolism; Interleukin-1beta - metabolism; Interleukin-1β; Macrophages - immunology; Macrophages - virology; Primary Cell Culture; Protein Binding; Pyroptosis
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2017.10.044

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.