SIGIRR plays a dual role in zebrafish infected with Edwardsiella piscicida: Boosting digestive system wellness and mitigating inflammation

Abstract

Single immunoglobulin interleukin-1 receptor-associated protein (SIGIRR) negatively regulates the inflammatory response induced by bacterial infection by inhibiting the excessive synthesis of inflammatory mediators and overactivation. This inhibitory mechanism reduces the fish's susceptibility to pathogens and enhances survival rates. Zebrafish lacking the SIGIRR gene were generated using CRISPR/Cas9 gene knockout technology. In a zebrafish model infected with Edwardsiella piscicida, researchers found that SIGIRR gene deletion led to a significant increase in the activation of both inflammatory and anti-inflammatory factors. This deletion also resulted in intestinal villus epithelium damage, epithelial shedding, separation of the epithelium and lamina propria, and a severe reduction in goblet cells. After E. piscicida infection, the survival rate of SIGIRR^−/− zebrafish was significantly reduced, and the number of E. piscicida in the body was also significantly increased. Intestinal acid phosphatase activity in SIGIRR^−/− zebrafish was markedly elevated compared to wild-type (WT) zebrafish. Furthermore, the intestinal mucosal layer and villus thickness in SIGIRR^−/− zebrafish were reduced compared to WT zebrafish. The enzymatic activities of lipase and lysozyme in the intestines of SIGIRR^−/− zebrafish were significantly lower than in WT zebrafish. This study reveals the detrimental effects of SIGIRR gene deletion on the intestinal health of zebrafish, leading to decreased innate immune capacity and increased susceptibility to bacterial infections.