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

Ka Tik Cheung, Daniel Man yuen Sze, Kwok Hung Chan, Hang Mei Polly Leung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

13 Citations (Scopus)

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.
Original languageEnglish
JournalImmunobiology
DOIs
Publication statusAccepted/In press - 1 Jan 2017

Keywords

  • Caspase-4
  • Dengue virus
  • Inflammasome
  • Interleukin-1β
  • Pyroptosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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