Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico.
Int J Parasitol. 2010 Aug 1;40(9):1051-62. doi: 10.1016/j.ijpara.2010.02.016. Epub 2010 Mar 30.
In cysticercosis, a parasitic disease caused by cestodes, the details of early interactions between parasite antigens and innate cells from the host are not well understood. In this study, the role of cestode-conditioned dendritic cells (DCs) in priming Th1 versus Th2 responses to bystander antigen was examined by using CD11c(+) DCs as antigen-presenting cells and naive CD4(+) DO11.10 lymphocytes specific to ovalbumin (OVA) as responding cells. No conventional maturation was induced in DCs exposed to Taenia crassiceps excreted/secreted antigens (TcES). The ability of TcES to affect Toll-like receptor (TLR)-mediated maturation and the pro-inflammatory response was analyzed by co-pulsing DCs with TcES and TLR ligands. DCs exposed to TcES blocked TLR4, TLR9 and Toxoplasma soluble antigen-induced phenotypic maturation. TcES-exposed DCs also blocked secretion of pro-inflammatory cytokines and alloreactive T cell proliferation, while preserving IL-10 production. DCs pulsed with TcES+OVA suppressed IFN-gamma, whereas they induced greater IL-4 production by CD4(+) DO11.10 cells. TcES with chemically-altered glycans failed to modulate TLR-mediated activation of DCs and their Th1-inhibitng ability, which was STAT6-independent. Our results reflect the capacity of TcES glyco-antigens to modulate Th1-type and inflammatory responses mediated through DC activation.
在由绦虫引起的囊尾蚴病中,宿主固有细胞与寄生虫抗原的早期相互作用的细节尚不清楚。在这项研究中,通过将 CD11c(+) DC 作为抗原呈递细胞,将对卵清蛋白 (OVA) 具有特异性的幼稚 CD4(+) DO11.10 淋巴细胞作为反应细胞,研究了绦虫条件化树突状细胞 (DC) 在启动旁观者抗原的 Th1 与 Th2 反应中的作用。暴露于阔节裂头绦虫排泄/分泌抗原 (TcES) 的 DC 未诱导常规成熟。通过将 DC 与 TcES 和 TLR 配体共同脉冲,分析了 TcES 影响 TLR 介导的成熟和促炎反应的能力。暴露于 TcES 的 DC 阻断了 TLR4、TLR9 和弓形虫可溶性抗原诱导的表型成熟。TcES 暴露的 DC 还阻断了促炎细胞因子的分泌和同种反应性 T 细胞的增殖,同时保留了 IL-10 的产生。用 TcES+OVA 脉冲的 DC 抑制了 IFN-γ的产生,而诱导了更多的 CD4(+) DO11.10 细胞产生 IL-4。化学改变糖基的 TcES 未能调节 TLR 介导的 DC 激活及其抑制 Th1 的能力,这与 STAT6 无关。我们的结果反映了 TcES 糖抗原调节通过 DC 激活介导的 Th1 型和炎症反应的能力。