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Pyroptosis Mediates Neutrophil Extracellular Trap Formation during Bacterial Infection in Zebrafish

2021; American Association of Immunologists; Volume: 206; Issue: 8 Linguagem: Inglês

10.4049/jimmunol.2001335

1550-6606

Weijie Chen, Jingjing Zhao, Di Mu, Zhuang Wang, Qin Liu, Yuanxing Zhang, Dahai Yang,

Immune Response and Inflammation

Abstract The formation of neutrophil extracellular trap (NET) is a critical host defense when neutrophils migrate to infection sites. Pyroptosis is a newly identified programmed cell death, which is tightly regulated by inflammasome activation. However, the mechanism of pyroptotic signaling participating in NET production remains to be elucidated. In this study, the zebrafish larvae otic vesicle microinjection model was used to infect larvae with hemolysin-overexpressing Edwardsiella piscicida (EthA+), and a rapid migration of neutrophils to infection sites was observed. Intriguingly, EthA+ infection effectively induced significant neutrophil membrane rupture in vivo, which was dependent on caspase-B (caspy2) and gasdermin Eb (GSDMEb) but not caspase-A or gasdermin Ea. Specifically, the EthA+ E. piscicida infection induced pyroptosis along with NETosis in vitro, and depletion of either caspy2 or GSDMEb impaired NET formation in vivo. Consequently, inhibition of the caspy2–GSDMEb axis-gated NETosis impaired bacterial clearance in vivo. Altogether, these data provide evidence that teleost fish innate immune cells, including neutrophils, express features of pyroptosis that are critical for NETosis in teleost innate immunity.