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Processing of zebrafish interleukin-1 beta during Francisella noatunensis infection: Roles of inflammatory caspases

Infection and Immunity

By:
, ,
DOI: 10.1128/​IAI.00543-12

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Abstract

The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1ß) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1ß is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1ß. Although zebrafish encode orthologs of IL-1ß and inflammatory caspases, the processing of IL-1ß 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-1ß processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1ß processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1ß into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1ß, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1ß in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.

Additional Publication Details

Publication type:
Article
Publication Subtype:
Journal Article
Title:
Processing of zebrafish interleukin-1 beta during Francisella noatunensis infection: Roles of inflammatory caspases
Series title:
Infection and Immunity
DOI:
10.1128/​IAI.00543-12
Volume
80
Issue:
8
Year Published:
2012
Language:
English
Publisher:
American Society for Microbiology
Publisher location:
Washington, D.C.
Contributing office(s):
Western Fisheries Research Center
Description:
8 p.
Larger Work Type:
Article
Larger Work Subtype:
Journal Article
Larger Work Title:
Infection and Immunity
First page:
2878
Last page:
2885