MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory of Biocontrol, School of Life Sciences, Guangzhou, People's Republic of China.
PLoS One. 2013;8(2):e52088. doi: 10.1371/journal.pone.0052088. Epub 2013 Feb 6.
The Toll-like receptor (TLR)-mediated NF-κB pathway is tightly controlled because overactivation may result in severe damage to the host, such as in the case of chronic inflammatory diseases and cancer. In mammals, sterile-alpha and armadillo motif-containing protein (SARM) plays an important role in negatively regulating this pathway. While Caenorhabditis elegans SARM is crucial for an efficient immune response against bacterial and fungal infections, it is still unknown whether Drosophila SARM participates in immune responses. Here, Litopenaeus vannamei SARM (LvSARM) was cloned and functionally characterized. LvSARM shared signature domains with and exhibited significant similarities to mammalian SARM. Real-time quantitative PCR analysis indicated that the expression of LvSARM was responsive to Vibrio alginolyticus and white spot syndrome virus (WSSV) infections in the hemocyte, gill, hepatopancreas and intestine. In Drosophila S2 cells, LvSARM was widely distributed in the cytoplasm and could significantly inhibit the promoters of the NF-κB pathway-controlled antimicrobial peptide genes (AMPs). Silencing of LvSARM using dsRNA-mediated RNA interference increased the expression levels of Penaeidins and antilipopolysaccharide factors, which are L.vannamei AMPs, and increased the mortality rate after V. alginolyticus infection. Taken together, our results reveal that LvSARM may be a novel component of the shrimp Toll pathway that negatively regulates shrimp AMPs, particularly Penaeidins and antilipopolysaccharide factors.
Toll 样受体 (TLR)-介导的 NF-κB 通路受到严格控制,因为过度激活可能会导致宿主严重受损,例如在慢性炎症性疾病和癌症的情况下。在哺乳动物中,无菌-α和角蛋白结构域蛋白 (SARM) 在负调控该通路方面发挥着重要作用。虽然秀丽隐杆线虫 SARM 对于有效抵抗细菌和真菌感染的免疫反应至关重要,但尚不清楚果蝇 SARM 是否参与免疫反应。在这里,克隆并功能表征了凡纳滨对虾 SARM (LvSARM)。LvSARM 与哺乳动物 SARM 具有特征性结构域,并表现出显著的相似性。实时定量 PCR 分析表明,LvSARM 的表达对副溶血弧菌和白斑综合征病毒 (WSSV) 在血细胞、鳃、肝胰腺和肠中的感染有反应。在果蝇 S2 细胞中,LvSARM 广泛分布在细胞质中,并能显著抑制 NF-κB 通路控制的抗菌肽基因 (AMPs) 的启动子。用 dsRNA 介导的 RNA 干扰沉默 LvSARM 会增加对虾抗菌肽,尤其是 Penaeidins 和抗脂多糖因子的表达水平,并增加副溶血弧菌感染后的死亡率。综上所述,我们的结果表明,LvSARM 可能是虾 Toll 途径的一个新组成部分,它负调控虾 AMPs,特别是 Penaeidins 和抗脂多糖因子。