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Eosinophils Control Liver Damage by Modulating Immune Responses Against Fasciola hepatica
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2020-08-19 , DOI: 10.3389/fimmu.2020.579801
Sofía Frigerio 1 , Valeria da Costa 1 , Monique Costa 1 , María Florencia Festari 1 , Mercedes Landeira 1 , Santiago A Rodríguez-Zraquia 1 , Steffen Härtel 2 , Jorge Toledo 2 , Teresa Freire 1
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Eosinophils are granulocytes that participate in the defense against helminth parasites and in hypersensitivity reactions. More recently, eosinophils were shown to have other immunomodulatory functions, such as tissue reparation, metabolism regulation, and suppression of Th1 and Th17 immune responses. In the context of parasitic helminth infections, eosinophils have a controversial role, as they can be beneficial or detrimental for the host. In this work, we investigate the role of eosinophils in an experimental infection in mice with the trematode parasite Fasciola hepatica, which causes substantial economical losses around the world due to the infection of livestock. We demonstrate that eosinophils are recruited to the peritoneal cavity and liver from F. hepatica-infected mice and this recruitment is associated with increased levels of CCL11, TSLP, and IL-5. Moreover, the characterization of peritoneal and hepatic eosinophils from F. hepatica-infected mice showed that they express distinctive molecules of activation and cell migration. Depletion of eosinophils with an anti-Siglec-F antibody provoked more severe clinical signs and increased liver damage than control animals which were accompanied by an increase in the production of IL-10 by hepatic and splenic CD4+ T cells. In addition, we also report that eosinophils participate in the modulation of humoral immune responses during F. hepatica infection, contributing to their degranulation. In conclusion, we demonstrate that eosinophils are beneficial for the host during F. hepatica infection, by limiting the production of IL-10 by specific CD4+ T cells and favoring eosinophil degranulation induced by specific antibodies. This work contributes to a better understanding of the role of eosinophils in parasitic helminth infections.



中文翻译:

嗜酸性粒细胞通过调节对费氏肝片的免疫应答来控制肝损伤

嗜酸性粒细胞是参与防御蠕虫寄生虫和超敏反应的粒细胞。最近,嗜酸性粒细胞被证明具有其他免疫调节功能,例如组织修复,代谢调节以及抑制Th1和Th17免疫反应。在寄生性蠕虫感染的情况下,嗜酸性粒细胞具有争议性的作用,因为它们可能对宿主有益或有害。在这项工作中,我们调查嗜酸性粒细胞在吸虫性寄生虫小鼠中的实验感染中的作用肝片吸虫,由于牲畜的感染,在世界范围内造成重大的经济损失。我们证明嗜酸性粒细胞被募集至腹膜腔和肝脏肝炎镰孢感染的小鼠,这种募集与CCL11,TSLP和IL-5水平升高有关。此外,腹膜和肝嗜酸性粒细胞的特征肝炎镰孢被感染的小鼠显示它们表达了独特的激活和细胞迁移分子。与对照动物相比,抗Siglec-F抗体消耗的嗜酸性粒细胞引起更严重的临床体征,并增加了肝损害,同时伴随着肝和脾CD4 + T细胞IL-10的产生增加。此外,我们还报告了嗜酸性粒细胞在免疫过程中参与体液免疫反应的调节肝炎镰孢感染,导致其脱粒。总之,我们证明了嗜酸性粒细胞在宿主中对宿主有益肝炎镰孢通过限制特异性CD4 + T细胞产生IL-10并促进特异性抗体诱导的嗜酸性粒细胞脱粒,可以预防感染。这项工作有助于更好地了解嗜酸性粒细胞在寄生虫蠕虫感染中的作用。

更新日期:2020-09-20
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