Roles of Inflammatory Caspases during Processing of Zebrafish Interleukin-1β in Francisella noatunensis Infection
- Authors
- Vojtech, L.N., Scharping, N., and Hansen, J.D.
- ID
- ZDB-PUB-120630-4
- Date
- 2012
- Source
- Infection and Immunity 80(8): 2878-2885 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Caspases/genetics
- Caspases/metabolism*
- Francisella/classification*
- Gene Expression Regulation
- Gram-Negative Bacterial Infections/metabolism
- Gram-Negative Bacterial Infections/microbiology*
- HEK293 Cells
- Humans
- Inflammation/enzymology*
- Interleukin-1beta/genetics
- Interleukin-1beta/metabolism*
- Molecular Sequence Data
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 22689811 Full text @ Infect. Immun.
The interleukin 1 family of cytokines are essential for the control of pathogenic microbes, but are also responsible for devastating auto-immune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome; a multiprotein complex that forms in the cytosol which results in the activation of inflammatory caspase (caspase-1), and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase-1 or pan-caspase inhibitors considerably abrogates IL-1β processing. Similar to mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase-A and caspase-B, are both able to cleave IL-1β, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.