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β-防御素:硬骨鱼类中的灵巧救星。

β-Defensin: An adroit saviour in teleosts.

作者信息

Das Sweta, Pradhan Chiranjiv, Pillai Devika

机构信息

Department of Aquatic Animal Health & Management, Kerala University of Fisheries and Ocean Studies, Kochi, Kerala, India.

Department of Aquaculture, Kerala University of Fisheries and Ocean Studies, Kochi, Kerala, India.

出版信息

Fish Shellfish Immunol. 2022 Apr;123:417-430. doi: 10.1016/j.fsi.2022.03.017. Epub 2022 Mar 22.

DOI:10.1016/j.fsi.2022.03.017
PMID:35331882
Abstract

β-Defensin (BD) is an important first line innate defense molecule with potent antimicrobial and immunomodulatory activities in fish. The signatures of β-defensins are the presence of a net cationic charge and three intramolecular disulfide bonds mediated by six conserved cysteines. It consists of three exons and two introns. The signal peptide is usually conserved and sequence divergence is mostly seen in mature peptide region. The diverse amino acid sequences of matured peptide contribute to a strong positive selection and broad-spectrum antimicrobial activity. It is constitutively expressed in both mucosal as well as systemic sites. Increased expression of β-defensin was mostly reported in bacterial and viral infections in fish. Its role during parasitic and fungal infections is yet to be investigated. β-Defensin isoforms such as BD-1, BD-2, BD-3, BD-4 and BD-5 can be witnessed even in early developmental days to different pathogenic exposure in fish. β-Defensins possess adjuvant properties to enhance antigen-specific immunity promoting both cellular and humoral immune response. It significantly reduces/increases bacterial colonization or viral copy numbers when overexpressed/knockdown. Based on its chemotactic and activating potentials, it can contribute to both innate and adaptive immune responses. With mediated expression, it can also control inflammation. It is potent governing resistance in early developmental days as well. Its expression in pituitary and testis suggests its participation in reproduction and endocrine regulation in fish. Overall, β-defensins is an important member of antimicrobial peptides (AMPs) with multifunctional role in general homeostasis and to pathogen exposure possessing tremendous therapeutic approaches.

摘要

β-防御素(BD)是鱼类中一种重要的一线固有防御分子,具有强大的抗菌和免疫调节活性。β-防御素的特征是存在净阳离子电荷以及由六个保守半胱氨酸介导的三个分子内二硫键。它由三个外显子和两个内含子组成。信号肽通常是保守的,序列差异大多出现在成熟肽区域。成熟肽多样的氨基酸序列导致强烈的正选择和广谱抗菌活性。它在黏膜和全身部位均组成性表达。鱼类在细菌和病毒感染时大多报道有β-防御素表达增加。其在寄生虫和真菌感染中的作用尚待研究。即使在鱼类发育早期,面对不同病原体暴露时,也能观察到BD-1、BD-2、BD-3、BD-4和BD-5等β-防御素亚型。β-防御素具有佐剂特性,可增强抗原特异性免疫,促进细胞免疫和体液免疫反应。过表达/敲低时,它能显著减少/增加细菌定植或病毒拷贝数。基于其趋化和激活潜能,它可参与固有免疫和适应性免疫反应。通过介导表达,它还能控制炎症。在发育早期它也具有强大的抗性调控作用。其在垂体和睾丸中的表达表明它参与鱼类的繁殖和内分泌调节。总体而言,β-防御素是抗菌肽(AMPs)的重要成员,在维持一般内环境稳定以及应对病原体暴露方面具有多功能作用,拥有巨大的治疗应用前景。

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