Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Sci Rep. 2017 Jan 12;7:40615. doi: 10.1038/srep40615.
Fasciolosis is a trematode zoonosis of interest in public health and cattle production. We report here the immunostimulatory effect of a 66 mer mucin-like peptide from Fasciola hepatica (Fhmuc), which synergizes with lipopolysaccharide (LPS) to promote dendritic cell (DC) maturation, endowing these cells with Th1-polarizing capacity. Exposure of DCs to Fhmuc in presence of LPS induced enhanced secretion of pro-inflammatory cytokines and expression of co-stimulatory molecules by DCs, promoting their T cell stimulatory capacity and selectively augmenting IFN-γ secretion by allogeneic T cells. Furthermore, exposure of DCs to Fhmuc augmented LPS-induced Toll-like receptor (TLR) 4 expression on the cell surface. Finally, Fhmuc-conditioned DCs induced parasite specific-adaptive immunity with increased levels of IFN-γ secreted by splenocytes from vaccinated animals, and higher parasite-specific IgG antibodies. However, Fhmuc-treated DC conferred modest protection against F. hepatica infection highlighting the potent immuno-regulatory capacity of the parasite. In summary, this work highlights the capacity of a mucin-derived peptide from F. hepatica to enhance LPS-maturation of DCs and induce parasite-specific immune responses with potential implications in vaccination and therapeutic strategies.
片形吸虫病是一种在公共卫生和牛生产中具有重要意义的吸虫动物传染病。我们在这里报告了从肝片形吸虫(Fasciola hepatica)中提取的一种 66 个氨基酸的粘蛋白样肽(Fhmuc)的免疫刺激作用,它与脂多糖(LPS)协同作用促进树突状细胞(DC)成熟,赋予这些细胞 Th1 极化能力。在 LPS 的存在下,Fhmuc 暴露于 DC 中会诱导 DC 分泌更多的促炎细胞因子和共刺激分子,增强其 T 细胞刺激能力,并选择性地增加同种异体 T 细胞的 IFN-γ分泌。此外,Fhmuc 暴露于 DC 中会增强 LPS 诱导的细胞表面 Toll 样受体(TLR)4 的表达。最后,Fhmuc 调理的 DC 诱导寄生虫特异性适应性免疫,接种动物的脾细胞分泌的 IFN-γ水平升高,寄生虫特异性 IgG 抗体水平升高。然而,Fhmuc 处理的 DC 对肝片形吸虫感染的保护作用有限,这突出了寄生虫的强大免疫调节能力。总之,这项工作强调了来自肝片形吸虫的粘蛋白衍生肽增强 LPS 成熟 DC 的能力,并诱导寄生虫特异性免疫反应,这可能对疫苗接种和治疗策略具有重要意义。