Laboratorio de Diagnóstico y Terapia, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile.
Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile.
Int J Mol Sci. 2024 Jun 8;25(12):6346. doi: 10.3390/ijms25126346.
The innate immune response in , mediated by pattern recognition receptors (PRRs), is crucial for defending against pathogens. This study examined DDX41 protein functions as a cytosolic/nuclear sensor for cyclic dinucleotides, RNA, and DNA from invasive intracellular bacteria. The investigation determined the existence, conservation, and functional expression of the gene in . In silico predictions and experimental validations identified a single gene on chromosome 5 in , showing 83.92% homology with its human counterpart. Transcriptomic analysis in salmon head kidney confirmed gene transcriptional integrity. Proteomic identification through mass spectrometry characterized three unique peptides with 99.99% statistical confidence. Phylogenetic analysis demonstrated significant evolutionary conservation across species. Functional gene expression analysis in SHK-1 cells infected by and indicated significant upregulation of DDX41, correlated with increased proinflammatory cytokine levels and activation of and interferon signaling pathways. In vivo studies corroborated DDX41 activation in immune responses, particularly when was challenged with , underscoring its potential in enhancing disease resistance. This is the first study to identify the DDX41 pathway as a key component in innate immune response to invading pathogens, establishing a basis for future research in salmonid disease resistance.
固有免疫反应由模式识别受体 (PRRs) 介导,对于抵御病原体至关重要。本研究探讨了 DDX41 蛋白作为胞质/核传感器,对侵袭性细胞内细菌的环二核苷酸、RNA 和 DNA 的作用。该研究确定了 在 中 的存在、保守性和功能表达。通过计算机预测和实验验证,在 5 号染色体上发现了一个 基因,其与人类对应物的同源性为 83.92%。在三文鱼头肾中的转录组分析证实了基因转录的完整性。通过质谱进行的蛋白质组学鉴定确定了三个具有 99.99%统计置信度的独特肽。系统发育分析表明,物种间存在显著的进化保守性。在 感染的 SHK-1 细胞中进行的功能性基因表达分析表明,DDX41 的表达显著上调,与促炎细胞因子水平的升高以及 和干扰素信号通路的激活相关。体内研究证实了 DDX41 在免疫反应中的激活,特别是当 受到 挑战时,这突显了它在增强鱼类疾病抵抗力方面的潜力。这是首次确定 DDX41 途径作为 固有免疫反应抵抗入侵病原体的关键组成部分的研究,为鲑鱼疾病抵抗力的未来研究奠定了基础。