AUTHOR=Qi Zhitao , Yan Dong , Cao Lu , Xu Yang , Chang Mingxian 

TITLE=Zebrafish BID Exerts an Antibacterial Role by Negatively Regulating p53, but in a Caspase-8-Independent Manner

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.707426

DOI=10.3389/fimmu.2021.707426

ISSN=1664-3224

ABSTRACT=<p>Bid (BH3-interacting domain death agonist), a member of the Bcl-2 family, plays a crucial role in the initiation of apoptosis. Independent of its apoptotic function, Bid is also involved in the regulation of inflammation and innate immunity. However, the role of Bid during bacterial pathogen infection remains unclear. In the present study, <italic>Bid</italic> of zebrafish (<italic>Dario rerio</italic>) was cloned and its functions during <italic>Edwardsiella ictaluri</italic> infection were investigated. Zebrafish Bid enhances the apoptosis rate of <italic>Epithelioma papulosum cyprini</italic> (EPC) cells following <italic>E. ictaluri</italic> infection. Importantly, <italic>in vitro</italic> and <italic>in vivo</italic> bacterial invasion assays showed that overexpressed Bid could significantly inhibit the invasion and proliferation of <italic>E. ictaluri</italic>. Real-time qPCR analysis revealed that p53 gene expression was downregulated in embryos microinjected with Bid-FLAG. Further, <italic>in vitro</italic> and <italic>in vivo</italic> bacterial invasion assays showed that overexpressed p53 increased the invasion and proliferation of <italic>E. ictaluri</italic>. Moreover, the invasion and proliferation of <italic>E. ictaluri</italic> were inhibited when co-overexpressing Bid and p53 <italic>in vivo</italic> and <italic>in vitro</italic>. Further, the numbers of <italic>E. ictaluri</italic> in larvae treated with Z-IETD-FMK (caspase-8 inhibitor) were higher than those of larvae without Z-IETD-FMK treatment, while the number of <italic>E. ictaluri</italic> in larvae microinjected with <italic>bid</italic>-Flag decreased significantly, even if the larvae were treated in advance with Z-IETD-FMK. Collectively, our study demonstrated a novel antibacterial activity of fish Bid, providing evidence for understanding the function of apoptosis associated gene in pathogen infection.</p>