Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated
Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated
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DOI：
10.1016/j.ijpara.2012.10.021
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发表时间：
2013-03-01
影响因子：
4
通讯作者：
van Die, Irma
中科院分区：
文献类型：
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作者：
Klaver, Elsenoor J.;Kuijk, Loes M.;van Die, Irma
人单核细胞来源的树突状细胞（DC）在与猪鞭虫（Trichuris suis）的可溶性产物（SP）直接接触后显示出显著的表型变化，猪鞭虫是一种实验性地用于治疗以改善克罗恩病和多发性硬化症患者的炎症的猪鞭虫。这些变化可能有助于观察到的T辅助细胞2（Th2）应答的诱导和Toll样受体（TLR）诱导的Th1和Th17应答的抑制。猪链球菌本文证明T.猪SP显著地有助于抑制脂多糖（LPS）诱导的DC中多种细胞因子和趋化因子的表达，所述细胞因子和趋化因子包括重要的促炎介质，例如TNF-α、IL-6、IL-12、α-光毒素（LTA）、C-C基序配体（CCL）2、C-X-C基序配体（CXCL）9和CXCL 10。此外，数据显示人DC强烈结合T.猪SP-聚糖通过C型凝集素受体（CLRs）、甘露糖受体（MR）和DC特异性ICAM-3抓取非整联蛋白（DC-SIGN）。DC与T.猪的聚糖可能涉及甘露糖型聚糖，而不是岩藻糖基化聚糖，这与DC结合人类寄生虫曼氏血吸虫的可溶性卵抗原不同。此外，巨噬细胞半乳糖型凝集素（MGL）识别T。猪SP，这可能有助于与未成熟的DC或其他表达MGL的免疫细胞如巨噬细胞的相互作用。T.猪聚糖与人DC的TLR可能对于T. suis抑制人DC的促炎表型。T.猪诱导的人DC功能的调节是聚糖介导的，这是新颖的，并且表明蠕虫聚糖有助于在广泛的人炎性疾病中抑制炎症。(C)2012年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
Human monocyte-derived dendritic cells (DCs) show remarkable phenotypic changes upon direct contact with soluble products (SPs) of Trichuris suis, a pig whipworm that is experimentally used in therapies to ameliorate inflammation in patients with Crohn's disease and multiple sclerosis. These changes may contribute to the observed induction of a T helper 2 (Th2) response and the suppression of Toll-like receptor (TLR)-induced Th1 and Th17 responses by human DCs primed with T. suis SPs. Here it is demonstrated that glycans of T. suis SPs contribute significantly to the suppression of the lipopolysaccharide (LPS)induced expression in DCs of a broad variety of cytokines and chemokines, including important proinflammatory mediators such as TNF-alpha, IL-6, IL-12, lymphotoxin alpha (LTA), C-C Motif Ligand (CCL)2, C-X-C Motif Ligands (CXCL)9 and CXCL10. In addition, the data show that human DCs strongly bind T. suis SP-glycans via the C-type lectin receptors (CLRs) mannose receptor (MR) and DC-specific ICAM-3-grabbing non-integrin (DC-SIGN). The interaction of DCs with T. suis glycans likely involves mannose-type glycans, rather than fucosylated glycans, which differs from DC binding to soluble egg antigens of the human worm parasite, Schistosoma mansoni. In addition, macrophage galactose-type lectin (MGL) recognises T. suis SPs, which may contribute to the interaction with immature DCs or other MGL-expressing immune cells such as macrophages. The interaction of T. suis glycans with CLRs of human DCs may be essential for the ability of T. suis to suppress a pro-inflammatory phenotype of human DCs. The finding that the T. suis-induced modulation of human DC function is glycan-mediated is novel and indicates that helminth glycans contribute to the dampening of inflammation in a wide range of human inflammatory diseases. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.