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利用表达III型分泌系统蛋白EspB的乳酸乳球菌对小鼠免疫系统进行黏膜致敏以抵抗肠出血性大肠杆菌O157:H7 。

Mucosal priming of the murine immune system against enterohemorrhagic Escherichia coli O157:H7 using Lactococcus lactis expressing the type III secretion system protein EspB.

作者信息

Ahmed B, Loos M, Vanrompay D, Cox E

机构信息

Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.

出版信息

Vet Immunol Immunopathol. 2013 Mar 15;152(1-2):141-5. doi: 10.1016/j.vetimm.2012.09.019. Epub 2012 Sep 26.

Abstract

Enterohemorrhagic Escherichia coli (EHEC), particularly E. coli serotype O157:H7, has been responsible for multiple human outbreaks of hemorrhagic colitis and hemolytic uremic syndrome worldwide. Humans become infected by direct or indirect contact with faeces of asymptomatic EHEC shedding ruminants. Currently there is no human or animal vaccine available against EHEC infection. EHEC use a type III secretion system (T3SS) to colonize the intestine and therefore eliciting mucosal immunity against T3SS proteins could be a potential vaccination strategy. To develop such a mucosal vaccine, EspB - a significant member of the T3SS - was intracellularly expressed in Lactococcus lactis (LL-EspB) and this strain was used to immunize BALB/c mice orally. Ten days post-immunization, no specific antibody response was detected in serum or faeces of immunized mice. However, statistically significant (P<0.0001) levels of specific serum Ig and faecal IgA were detected after intraperitoneal boosting of the orally immunized mice with recombinant EspB. Our results show that oral administration of LL-EspB resulted in mucosal priming of BALB/c mice against the EHEC T3SS protein, EspB. Nevertheless, an optimized EspB expression in L. lactis may be required to improve the mucosal immune response.

摘要

肠出血性大肠杆菌(EHEC),尤其是O157:H7血清型大肠杆菌,在全球范围内引发了多起人类出血性结肠炎和溶血尿毒综合征疫情。人类通过直接或间接接触无症状排出EHEC的反刍动物粪便而感染。目前尚无针对EHEC感染的人用或兽用疫苗。EHEC利用III型分泌系统(T3SS)在肠道内定植,因此引发针对T3SS蛋白的黏膜免疫可能是一种潜在的疫苗接种策略。为了开发这种黏膜疫苗,T3SS的重要成员EspB在乳酸乳球菌(LL-EspB)中进行细胞内表达,并使用该菌株对BALB/c小鼠进行口服免疫。免疫后10天,在免疫小鼠的血清或粪便中未检测到特异性抗体反应。然而,在用重组EspB对口服免疫的小鼠进行腹腔加强免疫后,检测到特异性血清Ig和粪便IgA水平具有统计学意义(P<0.0001)。我们的结果表明,口服LL-EspB可使BALB/c小鼠针对EHEC T3SS蛋白EspB产生黏膜致敏。尽管如此,可能需要优化EspB在乳酸乳球菌中的表达以改善黏膜免疫反应。

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