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肠道黏膜中的中和抗体对于控制产志贺毒素菌引起的胃肠道感染至关重要。

Neutralizing antibodies in the intestinal mucosa are essential to control gastrointestinal infection by Shiga toxin-producing .

作者信息

Bernal Alan Mauro, Sosa Fernando Nicolás, Carpintero-Polanco Yina María, Cancino Camila Dara, Fernández-Brando Romina Jimena, Ramos María Victoria, Podhozer Ariel, Errea Agustina, Rumbo Martín, Palermo Marina Sandra

机构信息

Instituto de Medicina Experimental-CONICET-Academia Nacional de Medicina Ciudad Autónoma de Buenos Aires Argentina.

Instituto de Estudios Inmunológicos y Fisiopatológicos-CONICET-Universidad Nacional de La Plata La Plata Argentina.

出版信息

mLife. 2025 Aug 25;4(4):409-422. doi: 10.1002/mlf2.70026. eCollection 2025 Aug.

Abstract

Infections with Shiga toxin (Stx)-producing (STEC) strains can result in a wide range of clinical presentations. Despite STEC O157:H7 being the serotype most frequently associated with hemolytic uremic syndrome (HUS), in some patients, a self-limited gastrointestinal infection is observed. We have previously demonstrated that genetic differences between BALB/c and C57BL/6 mice account for a different outcome after an experimental gastrointestinal STEC O157:H7 infection, in which the better outcome observed in BALB/c mice was associated with a Th-2 biased immune response. The objective of this study was to determine the role of anti-STEC antibodies during STEC O157:H7 infections. We first demonstrated that the B-cell-dependent response triggered upon STEC O157:H7 infection is necessary to keep BALB/c mice healthy and reciprocally C57BL/6 mice pre-challenged with an Stx2-deficient STEC O157:H7 strain were able to survive, remaining healthy after a subsequent STEC O157:H7 infection. We further proved that anti-STEC O157:H7 antibodies raised after infection have binding specificity against STEC O157:H7 bacteria, recognize H7, and have neutralizing capacitiy, by interfering with important pathogenic mechanisms such as motility and adhesion to intestinal epithelial cells. We conclude that local and/or systemic specific antibodies against STEC mediate prevention of lethal complications during STEC O157:H7 infections.

摘要

感染产志贺毒素(Stx)的大肠杆菌(STEC)菌株可导致多种临床表现。尽管STEC O157:H7是最常与溶血尿毒综合征(HUS)相关的血清型,但在一些患者中,观察到的是自限性胃肠道感染。我们之前已经证明,BALB/c和C57BL/6小鼠之间的基因差异导致实验性胃肠道STEC O157:H7感染后出现不同的结果,其中在BALB/c小鼠中观察到的较好结果与偏向Th-2的免疫反应有关。本研究的目的是确定抗STEC抗体在STEC O157:H7感染过程中的作用。我们首先证明,STEC O157:H7感染引发的B细胞依赖性反应对于维持BALB/c小鼠的健康是必要的,相反,用缺乏Stx2的STEC O157:H7菌株预先攻击的C57BL/6小鼠能够存活,在随后的STEC O157:H7感染后保持健康。我们进一步证明,感染后产生的抗STEC O157:H7抗体对STEC O157:H7细菌具有结合特异性,识别H7,并具有中和能力,通过干扰诸如运动性和对肠上皮细胞的粘附等重要致病机制来实现。我们得出结论,针对STEC的局部和/或全身特异性抗体介导了STEC O157:H7感染期间对致命并发症的预防。

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