Guo Shuang-Shuang, Duan Yi-Meng, Wei Jun-Yuan, Gao Miao-Miao, Jin Ze-Yu, Zhang Hong-Wei, Xia Xiao-Hua, Zhang Xiao-Wen
College of Life Sciences, Henan Normal University, Xinxiang, Henan 453007, China.
Department of Nature Resources, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China.
Int J Biol Macromol. 2025 Aug;320(Pt 2):145835. doi: 10.1016/j.ijbiomac.2025.145835. Epub 2025 Jul 7.
C-reactive protein (CRP), an evolutionarily conserved short pentraxin, functions as a critical soluble pattern recognition receptor (PRR) in innate immunity and exhibits phylogenetic conservation from arthropods to mammals. In this study, we identified a CRP gene in Litopenaeus vannamei and designated it LvCRP. In vitro studies demonstrated that recombinant LvCRP (rLvCRP) exhibits broad-spectrum pathogen recognition through high-affinity binding to conserved bacterial surface components (LPS, PGN, and PCh), facilitated by its multimeric complex formation. Notably, rLvCRP activated and modulated complement-like proteins in crustacean immunity, highlighting its evolutionary connection to the complement system. In vivo investigations demonstrated that rLvCRP enhances host defense through two synergistic mechanisms: (1) augmenting hemocyte-mediated phagocytosis and pathogen clearance efficiency, and (2) coordinately upregulating key immune components including inflammatory factors, complement-like molecule, and downstream antimicrobial peptides (AMPs). Furthermore, rLvCRP promoted nuclear translocation of the NF-κB homolog LvDorsal in shrimp hemocytes and significantly enhanced survival rates during Vibrio infection, establishing its crucial regulatory role in antibacterial immunity. Collectively, these findings establish LvCRP as a pivotal immunomodulator that integrates pattern recognition, complement activation, and effector mechanisms, exhibiting dual functionality in both cellular (phagocytosis) and humoral (complement activation/AMP production) immunity. This study demonstrates the evolutionary significance of CRP as a multifunctional defense molecule in crustaceans and provides novel insights into invertebrate immune regulation.
C反应蛋白(CRP)是一种进化上保守的短五聚体蛋白,作为先天性免疫中的关键可溶性模式识别受体(PRR)发挥作用,并且从节肢动物到哺乳动物都表现出系统发育上的保守性。在本研究中,我们在凡纳滨对虾中鉴定出一个CRP基因,并将其命名为LvCRP。体外研究表明,重组LvCRP(rLvCRP)通过与保守的细菌表面成分(LPS、PGN和PCh)高亲和力结合,展现出广谱病原体识别能力,这得益于其多聚体复合物的形成。值得注意的是,rLvCRP激活并调节甲壳动物免疫中的补体样蛋白,突出了其与补体系统的进化联系。体内研究表明,rLvCRP通过两种协同机制增强宿主防御:(1)增强血细胞介导的吞噬作用和病原体清除效率,以及(2)协同上调包括炎症因子、补体样分子和下游抗菌肽(AMPs)在内的关键免疫成分。此外,rLvCRP促进了对虾血细胞中NF-κB同源物LvDorsal的核转位,并显著提高了弧菌感染期间的存活率,确立了其在抗菌免疫中的关键调节作用。总的来说,这些发现确立了LvCRP作为一种关键免疫调节剂的地位,它整合了模式识别、补体激活和效应机制,在细胞(吞噬作用)和体液(补体激活/AMP产生)免疫中均表现出双重功能。本研究证明了CRP作为甲壳动物中多功能防御分子的进化意义,并为无脊椎动物免疫调节提供了新的见解。