Favoretto Bruna C, Casabuono Adriana A C, Portes-Junior José A, Jacysyn Jacqueline F, Couto Alicia S, Faquim-Mauro Eliana L
Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil.
CIHIDECAR-Departmento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Mol Immunol. 2017 Jul;87:33-46. doi: 10.1016/j.molimm.2017.03.015. Epub 2017 Apr 10.
Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs.
蠕虫及其分泌/排泄产物可诱导产生耐受性免疫微环境。猪蛔虫提取物中的高分子量成分（PI）可下调针对卵清蛋白（OVA）的免疫反应。PI对树突状细胞（DC）具有直接作用，且不依赖于Toll样受体2、4和髓样分化因子88分子，因此可降低T淋巴细胞反应。在此，我们研究了PI中的糖缀合物以及C型凝集素受体（CLR）、树突状细胞特异性细胞间黏附分子-3抓取非整合素（DC-SIGN）和甘露糖受体（MR）在调节DC活性中的作用。我们的数据表明，PI上存在具有高甘露糖型和复合型N-连接寡糖链以及磷酸胆碱残基的糖缀合物。此外，这些N-连接糖缀合物可抑制脂多糖诱导的DC成熟。在预先用甘露聚糖、抗DC-SIGN和/或抗MR抗体孵育的DC上，PI-Alexa的结合和内化减少。与此一致的是，用甘露聚糖、抗DC-SIGN和/或抗MR抗体孵育DC可消除PI对这些细胞的下调作用。还观察到，阻断DC上的CLR、DC-SIGN和MR可逆转PI对体外T细胞增殖的抑制作用。因此，我们的数据表明DC-SIGN和MR参与了PI的N-糖基化成分对DC的识别及后续调节作用。
