Rodríguez Ernesto, Carasi Paula, Frigerio Sofía, da Costa Valeria, van Vliet Sandra, Noya Verónica, Brossard Natalie, van Kooyk Yvette, García-Vallejo Juan J, Freire Teresa
Grupo de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República , Montevideo , Uruguay.
Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam , Netherlands.
Front Immunol. 2017 Mar 15;8:264. doi: 10.3389/fimmu.2017.00264. eCollection 2017.
Fasciolosis, caused by and , is a trematode zoonosis of interest in public health and livestock production. Like other helminths, modulates the host immune response by inducing potent polarized Th2 and regulatory T cell immune responses and by downregulating the production of Th1 cytokines. In this work, we show that glycans increase Th2 immune responses by immunomodulating TLR-induced maturation and function of dendritic cells (DCs). This process was mediated by the macrophage Gal/GalNAc lectin (MGL) expressed on DCs, which recognizes the Tn antigen (GalNAc-Ser/Thr) on parasite components. More interestingly, we identified MGL-expressing CD11c cells in infected animals and showed that these cells are recruited both to the peritoneum and the liver upon infection. These cells express the regulatory cytokines IL-10, TNFα and TGFβ and a variety of regulatory markers. Furthermore, MGL CD11c cells expand parasite-specific Th2/regulatory cells and suppress Th1 polarization. The results presented here suggest a potential role of MGL in the immunomodulation of DCs induced by and contribute to a better understanding of the molecular and immunoregulatory mechanisms induced by this parasite.
由肝片吸虫引起的肝片吸虫病是一种在公共卫生和家畜生产方面备受关注的吸虫类人畜共患病。与其他蠕虫一样,肝片吸虫通过诱导强烈的极化Th2和调节性T细胞免疫反应以及下调Th1细胞因子的产生来调节宿主免疫反应。在这项研究中,我们发现肝片吸虫聚糖通过免疫调节Toll样受体(TLR)诱导的树突状细胞(DC)成熟和功能来增强Th2免疫反应。这一过程由DC上表达的巨噬细胞半乳糖/ N - 乙酰半乳糖胺凝集素(MGL)介导,该凝集素识别寄生虫成分上的Tn抗原(N - 乙酰半乳糖胺 - 丝氨酸/苏氨酸)。更有趣的是,我们在受感染动物中鉴定出表达MGL的CD11c细胞,并表明在肝片吸虫感染后,这些细胞会被募集到腹膜和肝脏。这些细胞表达调节性细胞因子白细胞介素 - 10(IL - 10)、肿瘤坏死因子α(TNFα)和转化生长因子β(TGFβ)以及多种调节性标志物。此外,表达MGL的CD11c细胞可扩增寄生虫特异性Th2 /调节性细胞并抑制Th1极化。本文展示的结果表明MGL在肝片吸虫诱导的DC免疫调节中具有潜在作用,有助于更好地理解这种寄生虫诱导的分子和免疫调节机制。