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

Abstract

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, Bid of zebrafish (Dario rerio) was cloned and its functions during Edwardsiella ictaluri infection were investigated. Zebrafish Bid enhances the apoptosis rate of Epithelioma papulosum cyprini (EPC) cells following E. ictaluri infection. Importantly, in vitro and in vivo bacterial invasion assays showed that overexpressed Bid could significantly inhibit the invasion and proliferation of E. ictaluri. Real-time qPCR analysis revealed that p53 gene expression was downregulated in embryos microinjected with Bid-FLAG. Further, in vitro and in vivo bacterial invasion assays showed that overexpressed p53 increased the invasion and proliferation of E. ictaluri. Moreover, the invasion and proliferation of E. ictaluri were inhibited when co-overexpressing Bid and p53 in vivo and in vitro. Further, the numbers of E. ictaluri 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 E. ictaluri in larvae microinjected with bid-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.

The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner

“…In addition, overexpression of BIRC2 significantly impaired larvae survival and inhibited apoptosis, which had the higher bacterial loads. The present study confirms that the antiapoptotic protein BIRC2 negatively regulates bacterial infection, which is consistent with our recent report showing that proapoptotic protein BID positively regulates bacterial infection ( 36 ). Together, these results suggest that apoptosis-related proteins may play an important role in the regulation of pathogen infections, in addition to their conserved function in apoptosis.…”

“…The interaction and co-localization between zebrafish BIRC2 and p53 were found in the cytoplasm of infected cells. Besides, BIRC2 overexpression markedly increased p53 levels in the case of E. piscicida infection, which was different from the suppression of proapoptotic protein BID on the p53 (36). Unexpectedly, zebrafish larvae overexpressed with BIRC2 presented the increased p53 levels, but resulted in an increased infection rate and bacterial growth and dissemination.…”

SIGIRR-caspase-8 signaling mediates endothelial apoptosis in Kawasaki disease

“…As is known, caspase-8 plays an important role in death receptor-mediated apoptosis [ 20 , 21 ]. To confirm whether endothelial cell apoptosis was regulated by casapase-8, caspase-8 activity was inhibited using a caspase-8-specific inhibitor, Z-IETD-FMK [ 22 ]. Results exhibited that addition of Z-IETD-FMK significantly reduced the percentage of apoptotic endothelial cells compared with KD group (Fig.…”

Natural killer cell-related gene signature predicts malignancy of glioma and the survival of patients

“…After the death receptors is activated, BID is cleaved by caspase-8 into an N-terminal p13 and a C-terminal truncated BID (tBID) which could transfers from cytoplasm to mitochondria and induces the release of cytochrome C, resulting in apoptosis [ 40 ]. Bid was also found to play crucial roles in inflammation and innate immunity by interplaying with nucleotide-binding and oligomerization (NOD) 1, NOD2, and the IκB kinase (IKK) complex [ 41 ].…”