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Linking murine resistance to secondary cystic echinococcosis with antibody responses targeting Echinococcus granulosus tegumental antigens.
Immunobiology ( IF 2.8 ) Pub Date : 2020-02-19 , DOI: 10.1016/j.imbio.2020.151916
Sebastián Miles 1 , Javier Magnone 1 , Marek Cyrklaff 2 , Paula Arbildi 1 , Friedrich Frischknecht 2 , Sylvia Dematteis 1 , Gustavo Mourglia-Ettlin 1
Affiliation  

Successful establishment of a parasite infection depends partially on the host intrinsic susceptibility to the pathogen. In cystic echinococcosis (CE), a zoonotic disease caused by the cestode parasite Echinococcus granulosus, the infection outcome in the murine model of secondary CE varies according to the mouse strain used. In this regard, intrinsic differences in susceptibility to the infection were previously reported for Balb/c and C57Bl/6 mice, being C57Bl/6 animals less permissive to secondary CE. Induction of parasite-specific antibodies has been suggested to play relevant roles in such susceptibility/resistance phenomena. Here, we report an in deep comparison of antibody responses induced in both mouse strains. Firstly, only C57Bl/6 mice were shown to induce specific-antibodies with efficient anti-parasite activities during early secondary CE. Then, through ImmunoTEM and Serological Proteome Analysis (SERPA), an evaluation of specific antibody responses targeting parasite tegumental antigens was performed. Both strategies showed that infected C57Bl/6 mice -unlike Balb/c animals- narrowed their IgG recognition repertoire against tegumental antigens, targeting fewer but potentially more relevant parasite components. In this sense, tegumental antigens recognition between Balb/c and C57Bl/6 mice, either by natural and/or induced antibodies, was analyzed through SERPA and MALDI-TOF/TOF studies. A total of 13 differentially recognized proteins (DRPs) uniquely targeted by antibodies from C57Bl/6 mice were successfully identified, wherein a subset of 7 DRPs were only recognized by infection-induced antibodies, suggesting their potential as natural protective antigens. In this regard, immunoinformatic analyses showed that such DRPs exhibited higher numbers of possible T cell epitopes towards the H-2-IAb haplotype, which is present in C57Bl/6 mice but absent in Balb/c animals. In summary, our results showed that the genetic predisposition to generate better T-dependent antibody responses against particular tegumental antigens might be a key factor influencing host susceptibility in the murine model of secondary CE.

中文翻译:

将鼠对继发性囊性棘球蚴病的抗性与针对细粒棘球绦虫外皮抗原的抗体反应联系起来。

寄生虫感染的成功建立部分取决于宿主对病原体的内在易感性。在囊性棘球蚴病 (CE) 中,这是一种由绦虫寄生虫细粒棘球绦虫引起的人畜共患病,继发性 CE 小鼠模型中的感染结果因使用的小鼠品系而异。在这方面,先前报道了 Balb/c 和 C57Bl/6 小鼠感染易感性的内在差异,即 C57Bl/6 动物对继发性 CE 的容忍度较低。已建议寄生虫特异性抗体的诱导在此类易感性/抗性现象中发挥相关作用。在这里,我们报告了对两种小鼠品系中诱导的抗体反应的深入比较。首先,只有 C57Bl/6 小鼠在早期继发性 CE 期间诱导具有有效抗寄生虫活性的特异性抗体。然后,通过免疫 TEM 和血清蛋白质组分析 (SERPA),对针对寄生虫外皮抗原的特异性抗体反应进行了评估。两种策略都表明,受感染的 C57Bl/6 小鼠 - 与 Balb/c 动物不同 - 缩小了它们针对外皮抗原的 IgG 识别库,针对较少但可能更相关的寄生虫成分。从这个意义上说,通过 SERPA 和 MALDI-TOF/TOF 研究分析了 Balb/c 和 C57Bl/6 小鼠之间通过天然和/或诱导抗体识别的外皮抗原。共成功鉴定了来自 C57Bl/6 小鼠的抗体唯一靶向的 13 种差异识别蛋白 (DRP),其中 7 个 DRP 的子集仅被感染诱导的抗体识别,表明它们具有作为天然保护性抗原的潜力。在这方面,免疫信息学分析表明,此类 DRP 对 H-2-IAb 单倍型表现出更多可能的 T 细胞表位,这在 C57Bl/6 小鼠中存在,但在 Balb/c 动物中不存在。总之,我们的结果表明,产生针对特定皮膜抗原的更好的 T 依赖性抗体反应的遗传倾向可能是影响继发性 CE 小鼠模型中宿主易感性的关键因素。它存在于 C57Bl/6 小鼠中,但不存在于 Balb/c 动物中。总之,我们的结果表明,产生针对特定皮膜抗原的更好的 T 依赖性抗体反应的遗传倾向可能是影响继发性 CE 小鼠模型中宿主易感性的关键因素。它存在于 C57Bl/6 小鼠中,但不存在于 Balb/c 动物中。总之,我们的结果表明,产生针对特定皮膜抗原的更好的 T 依赖性抗体反应的遗传倾向可能是影响继发性 CE 小鼠模型中宿主易感性的关键因素。
更新日期:2020-04-21
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