A dual-function interleukin-1 receptor couples bacterial recognition to MyD88-dependent NF-κB activation during...

The interleukin-1 receptor (IL-1R) is a key member of the Toll/interleukin-1 receptor superfamily that plays essential roles in inflammatory signaling and immune regulation in vertebrates. Unlike vertebrate IL-1Rs, which are primarily specialized for the recognition of endogenous IL-1 family cytokines, the biological functions of IL-1R in crustaceans remain poorly understood. In this study, we systematically investigated the immune function of IL-1R in the Pacific white shrimp (Penaeus vannamei) during Vibrio parahaemolyticus infection. Tissue distribution analysis revealed that IL-1R was predominantly expressed in hemocytes and was significantly induced following immune stimulation. Co-immunoprecipitation and AlphaFold-based structural modeling demonstrated that IL-1R interacted with the adaptor protein MyD88 through its intracellular Toll/interleukin-1 receptor (TIR) domain. Functional analyses showed that silencing IL-1R markedly impaired pathogen-induced NF-κB (Dorsal) nuclear translocation, indicating that IL-1R functions upstream of the MyD88-Dorsal signaling pathway. Notably, recombinant IL-1R exhibited broad-spectrum binding activity toward both Gram-positive and Gram-negative bacteria, revealing a pathogen-recognition function that has not been reported for vertebrate IL-1Rs. Furthermore, administration of soluble recombinant IL-1R significantly increased bacterial burden and mortality in infected shrimp, whereas RNA interference-mediated knockdown of IL-1R produced similar susceptibility phenotypes. Collectively, our findings revealed a previously unrecognized dual-function mechanism of crustacean IL-1R, acting both as a pathogen-recognition receptor and as a signaling receptor that activated the MyD88-Dorsal pathway to orchestrate antibacterial immunity. This study expands current understanding of IL-1R evolution and innate immune regulation in crustaceans and provides a potential molecular target for disease-resistant breeding and immune intervention strategies in shrimp aquaculture.