Sensing of Cytosolic LPS Through Caspy2 Pyrin Domain Mediates Noncanonical Inflammasome Activation in Zebrafish

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Aug 5

PMID 30076291

Citations 25

Authors

Dahai Yang

Xin Zheng

Shouwen Chen

Zhuang Wang

Wenting Xu

Jinchao Tan

Tianjian Hu

Mingyu Hou

Wenhui Wang

Zhaoyan Gu

Qiyao Wang

Ruilin Zhang

Yuanxing Zhang

Qin Liu

Affiliations

Soon will be listed here.

Abstract

The noncanonical inflammasome is critical for cytosolic sensing of Gram-negative pathogens. Here, we show that bacterial infection induces caspy2 activation in zebrafish fibroblasts, which mediates pyroptosis via a caspase-5-like activity. Zebrafish caspy2 binds directly to lipopolysaccharide via the N-terminal pyrin death domain, resulting in caspy2 oligomerization, which is critical for pyroptosis. Furthermore, we show that caspy2 is highly expressed in the zebrafish gut and is activated during infection. Knockdown of caspy2 expression impairs the ability of zebrafish to restrict bacterial invasion in vivo, and protects larvae from lethal sepsis. Collectively, our results identify a crucial event in the evolution of pattern recognition into the death domain superfamily-mediated intracellular lipopolysaccharide-sensing pathway in innate immunity.

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