金黄色葡萄球菌肠毒素中毒的免疫治疗策略

The Immunotherapy Strategies of Staphylococcus aureus Enterotoxin Poisoning

金黄色葡萄球菌肠毒素(staphylococcal enterotoxins,SEs)是由金黄色葡萄球菌(Staphylococcus aureus)分泌的一类具有呕吐活性的细菌外毒素,可引起严重的炎症反应和食物中毒。SEs具有超抗原活性,可与T细胞受体的可变区和MHC Ⅱ类分子形成三元复合物(TCR-SEs-MHC Ⅱ),直接刺激T淋巴细胞大量产生肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、白介素(interleukin,IL)-2、IL-6和γ干扰素(interferon γ,IFN-γ)等细胞因子,从而导致中毒性休克综合征(toxicshocksyndrome,TSS)。在临床常见的SEs中,肠毒素A(staphylococcalenterotoxin A,SEA)和肠毒素B(staphylococcal enterotoxin B,SEB)是出现频率最高、毒性最大、危害最严重的两种。目前尚没有针对SEs中毒治疗策略的综述性研究。本文首先概述了SEs的分类、结构及毒性作用,重点围绕SEA和SEB,分析了TCR-SEs-MHC II类分子相互作用位点,最后总结了针对SEs中毒的主动免疫疗法和被动免疫疗法,本文为SEs的深入研究提供了必要信息。

Staphylococcal enterotoxins(SEs)are kinds of bacterial exotoxins with vomiting activity secreted by S.aureus,which can cause diseases such as inflammation and food poisoning.SEs possess superantigen activity and can form ternary complexes with the variable region of T-cell receptor(TCR)and MHC class Ⅱ molecule,i.e.,TCR-SEs-MHC class Ⅱ molecule,which could directly stimulate up to 30% of T lymphocytes to produce a large numbers of cytokines such as tumor necrosis factor-α(TNF-α),interleukin 2(IL-2),IL-6,and interferon γ(IFN-γ),resulting in toxic shock syndrome(TSS).Among the common SEs,staphylococcal enterotoxin A(SEA)and staphylococcal enterotoxin B(SEB)are the most studied due to higher toxicity and frequency in reported incidents.Specially,about 70% of S.aureus food poisoning are caused by SEA,while,SEB was listed as an offensive biological warfare agent in 1960s.At present,there are few comprehensive review paper on treatment strategies for SEs poisoning.Hence,the review firstly introduces the classification,structure,and toxic effects of SEs,and then the ternary complexes of TCR-SEs-MHC class Ⅱ molecular interaction sites are analyzed focusing on SEA and SEB.Furthermore,we summarize the recent advance in the filed of active and passive immunotherapy for SEs poisoning around SEA and SEB.We highlight the state of art and new developments on active immunotherapy mainly includes attenuated vaccine,subunit vaccine and other vaccines and passive immunotherapy that is mainly based on monoclonal antibody and genetic engineering antibody.Finally,we discuss and prospect the current limitations and future development of immunotherapy for SEs including synthetic peptide vaccine,single cell technology and nanobody isolation.