Fernandez-Brando Romina Jimena, Cabrera Gabriel, Baschkier Ariela, Mejías María Pilar, Panek Cecilia Analia, Miliwebsky Elizabeth, Abrey-Recalde María Jimena, Bentancor Leticia Verónica, Ramos María Victoria, Rivas Marta, Palermo Marina Sandra
Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081 (C1425AUM), Buenos Aires, Argentina.
Med Microbiol Immunol. 2014 Jun;203(3):145-54. doi: 10.1007/s00430-013-0325-y. Epub 2014 Jan 8.
Hemolytic uremic syndrome (HUS) is the major complication of gastrointestinal infections with enterohemorrhagic Escherichia coli (EHEC) and is mediated by the production of Shiga toxins (Stx). Although it has been previously reported that not only HUS patients but healthy children have anti-Stx antibodies, very little is known about how these infections impact on mucosal immune system to generate a specific immune response. This work aimed to evaluate the immune responses elicited after a single oral dose of EHEC in a mouse model of HUS at weaning. We found sequential activation of T and B lymphocytes together with an increased percentage of IgA-bearing B cells in Peyer's patches and mesenteric lymph nodes. We also found fecal anti-EHEC IgA and serum anti-Stx2 IgG in EHEC-inoculated mice. Besides, these mice were partially protected against an intravenous challenge with Stx2. These data demonstrate that one episode of EHEC infection is enough to induce activation in the gut-associated lymphoid tissue, especially the B cell compartment, and lead to the production of specific IgA in mucosal tissue and the generation of systemic protection against Stx2 in a percentage of intragastrically inoculated mice. These data also support the epidemiologic observation that a second episode of HUS is very rare.
溶血尿毒综合征(HUS)是肠出血性大肠杆菌(EHEC)引起的胃肠道感染的主要并发症,由志贺毒素(Stx)的产生介导。尽管此前有报道称不仅HUS患者,健康儿童也有抗Stx抗体,但对于这些感染如何影响黏膜免疫系统以产生特异性免疫反应却知之甚少。这项研究旨在评估在断奶期的HUS小鼠模型中单次口服EHEC后引发的免疫反应。我们发现T和B淋巴细胞相继被激活,派尔集合淋巴结和肠系膜淋巴结中携带IgA的B细胞百分比增加。我们还在接种EHEC的小鼠中发现了粪便抗EHEC IgA和血清抗Stx2 IgG。此外,这些小鼠对Stx2静脉内攻击有部分保护作用。这些数据表明,一次EHEC感染足以诱导肠道相关淋巴组织(尤其是B细胞区室)激活,并导致黏膜组织中产生特异性IgA,且在一定比例的经胃内接种的小鼠中产生针对Stx2的全身保护作用。这些数据也支持了HUS第二次发作非常罕见的流行病学观察结果。