Jul 2026· Fish and Shellfish Immunology· pp.
111611
· 0 citations· 52 references
Medicine
TL;DR
Results indicated that maIRAK1BP1 played an important role in mediating host innate immune response to pathogen invasion, and disclosed the involvement of maIRAK1BP1 in NF-κB-mediated production of proinflammatory cytokines, which provided foundational insights into the conserved role of IRAK1BP1 in teleost immune regulation.
Abstract
Interleukin receptor-associated kinase (IRAK)-1 binding protein 1 (IRAK1BP1) is a vital factor in preventing dangerous overproduction of proinflammatory cytokines by the innate immune system. The structure and function of IRAK1BP1 have been well investigated in mammals, yet the piscine IRAK1BP1 is poorly understood. In the present study, the first teleost fish IRAK1BP1 from blunt snout bream, maIRAK1BP1, was identified and characterized, which was composed of a 750 bp open reading frame encoding a protein of 249 amino acids. Phylogenetic analysis indicated that maIRAK1BP1, is a novel member of IRAK1BP1 family and showed the highest similarity to that of grass carp (96.28%). Amino acid sequence analysis revealed that maIRAK1BP1 shared a conserved SIMPL domain. Spatial expression pattern analysis revealed that maIRAK1BP1 was constitutively expressed in various normal tissues including heart, spleen, head kidneys, gill, kidney, muscle, intestine and liver. The maIRAK1BP1 expression in immune-relevant tissues (liver, head kidneys and kidney) and caudal fin cells (MAF) were significantly up-regulated after LPS and bacteria injection. The result from subcellular localization analysis indicated that maIRAK1BP1 protein was localized in both the cytoplasm and nucleus of MAF cells, but predominantly existed in cytoplasm. The activity of NF-κB promoter could be inhibited by overexpression of maIRAK1BP1 in HEK-293T cells. Overexpression of maIRAK1BP1 in MAF cells inhibited dramatically the transcriptional expression level of lipopolysaccharide-induced proinflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α). In contrast, an increased expression of these cytokines was observed when maIRAK1BP1 was knocked down via siRNA. Taken together, these results indicated that maIRAK1BP1 played an important role in mediating host innate immune response to pathogen invasion, and disclosed the involvement of maIRAK1BP1 in NF-κB-mediated production of proinflammatory cytokines, which provided foundational insights into the conserved role of IRAK1BP1 in teleost immune regulation.
SiTRAF3 is identified as a pivotal scaffold protein in the echinoid innate immune system, as it significantly drove the promoter activities of nuclear factor kappa-B, activator protein-1, signal transducer and activator of transcription 3, along with multiple inflammatory cytokines and interferon-related elements.
Xiaolong Chu, Feng-Cheng Liu, Yingying Liu et al.· Fish and Shellfish Immunolog...· 0 citations
Type II interferon (IFN-γ) plays a central role in immune regulation in teleosts, but the signaling mechanisms mediated by its receptor subunits in teleosts remain unclear. This study investigated the immune regulatory network of Sebastes schlegelii (S. schlegelii) IFN-γ (SsIFN-γ) and the molecular functional characteristics of its receptor chains, SsIFNGR1 and SsIFNGR2. Transcriptome analysis of spleen after stimulation with recombinant SsIFN-γ protein revealed 5,402 differentially expressed genes, which were mainly concentrated in antigen processing and presentation, cytokine-cytokine receptor interactions, IL-17 signaling and apoptosis pathways. The sequence analysis indicated that both SsIFNGR1 (419 aa) and SsIFNGR2 (287 aa) possess conserved fibronectin type III (FN III) domains, signal peptides and transmembrane regions. Both receptors are widely expressed in tissues, with the highest expression levels in gills/intestine (SsIFNGR1) and spleen/gills (SsIFNGR2). Meanwhile, the mRNA expression of SsIFNGR1 and SsIFNGR2 were significantly upregulated following stimulation by bacteria, virus, poly(I:C), or rSsIFN-γ. Co-localization and co-immunoprecipitation experiments demonstrated that SsIFN-γ could interacts with SsIFNGR1 and SsIFNGR2. SsIFNGR1 and SsIFNGR2 enhance the expression of rSsIFN-γ-induced antiviral effector molecules (ISG15, Viperin, Mx) and signaling components (STAT1, SOCS1). In EPC cells, two receptors significantly enhance SsIFN-γ-mediated inhibition of carp spring viremia virus replication. In vivo, SsIFNGR1 and SsIFNGR2 alleviated intestinal pathological damage caused by Edwardsiella piscicida, accompanied by significant upregulation of pro-inflammatory cytokines, antimicrobial peptides (Hepcidin-1, TFPI-1) and JAK-STAT pathway genes. These findings characterize the IFN-γ signaling mechanism in teleosts and highlight the synergistic roles of these receptors in antiviral and antibacterial defenses, providing new insights for disease prevention and control in aquaculture.
Kai Yang, Nuo Sun, Zi-qi Wang et al.· Fish and Shellfish Immunolog...· 0 citations
Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is one of the regulatory subunits of protein phosphatase 1 (PP1). Current research on PPP1R3G is primarily focused on glycogen synthesis and lipid metabolism. However, the role of ppp1r3g in the innate immune response of fish has not been completely elucidated. This study demonstrated that ppp1r3g regulates RLR signaling pathway through interactions with Rig-I, Mda5, and Traf6. In parallel, Ppp1r3g inhibits platelet activation by regulating 14-3-3 zeta (14-3-3ζ) and consequently modulating the formation of the 14-3-3ζ-integrin-β3 (Itgb3) complex. In vivo analysis revealed that compared with the wild-type controls, ppp1r3g-null rare minnow (Gobiocypris rarus) and ppp1r3g-chimera grass carp (Ctenopharyngodon idella) exhibited significantly enhanced resistance to grass carp reovirus (GCRV), with markedly alleviated hemorrhagic symptoms post-infection. Furthermore, knockdown of ppp1r3g suppressed GCRV replication and upregulated type I interferon (IFN-1) expression in grass carp kidney (CIK) cells. Additionally, Ppp1r3g binds to the -ESKVFYLKMKGDYYRYL- fragment (EL17) of 14-3-3ζ via the Ser36/37 phosphorylation site located on the PP1c domain. This study also demonstrated that 14-3-3ζ interacts with Itgb3 through this fragment, indicating that Ppp1r3g competes with Itgb3 to bind 14-3-3ζ. Furthermore, Ppp1r3g dose-dependently promoted Itgb3 degradation via a proteolytic pathway. These findings indicate that Ppp1r3g negatively regulates innate antiviral immunity after GCRV stimulation and suppresses platelet and coagulation cascade activation by modulating the interaction between 14-3-3ζ and Itgb3 in fish.
Ru-Yi Wang, Man Zhou, Yuxuan Wang et al.· PLoS Pathogens· 0 citations
Deletion of MEX3B inhibited caspase-4 and gasdermin D activation, pyroptosis, and secretion of inflammasome-dependent inflammatory cytokines in human cell lines and murine primary macrophages and suggested that MEX3B is a pan-inflammasome regulator targeting inflammatory caspases.
Peng-Hua Wang, Jason G. Cahoon, Duo-Meng Yang et al.· Journal of Immunology· 0 citations
The RelA subunit is a core component of the nuclear factor-kappa B (NF-κB) family and plays a pivotal role in regulating immune and inflammatory responses across vertebrates and invertebrates. However, its functional role remains poorly defined in marine bivalves. In this study, a RelA homolog (RpRelA) was identified and functionally characterized in the Manila clam (Ruditapes philippinarum). The full-length cDNA of RpRelA is 2055 bp, encoding a 684-amino acid protein containing a conserved Rel homology domain (RHD) and an IPT domains. Both its tertiary structure and amino acid sequence are highly conserved across species. Phylogenetic analysis indicated that RpRelA clusters with invertebrate Rel family members. Quantitative real-time PCR (qRT-PCR) revealed that RpRelA is ubiquitously expressed in all examined tissues, with the highest expression levels detected in haemocytes and gills. Following V. parahaemolyticus challenge, both the mRNA and protein levels of RpRelA were significantly upregulated. Consistently, nuclear-cytoplasmic fractionation Western blot and immunofluorescence analyses confirmed its robust nuclear translocation upon bacterial infection. Furthermore, overexpression of RpRelA significantly upregulated pro-inflammatory genes (RpIL-17 and RpTNF) and caused severe gill inflammation, whereas its silencing suppressed their expression and alleviated the inflammatory response. Collectively, these results demonstrate that RpRelA, as a core NF-κB subunit, positively regulates the inflammatory response during V. parahaemolyticus infection in Manila clam, and provide new insights into the immune regulatory mechanism of bivalves against bacterial infection.
Hao-Dong Feng, Tian Yu, Jia-Xi Liang et al.· Fish and Shellfish Immunolog...· 0 citations
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.
Si-You Huang, Wan-Li Lu, Yuxin Shi et al.· Fish and Shellfish Immunolog...· 0 citations
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