Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
Ann N Y Acad Sci. 2012 Apr;1253:E1-E13. doi: 10.1111/j.1749-6632.2012.06618.x.
Helminth parasites bias host CD4(+) T helper (Th) cells toward Th2 responses, drive alternative activation of macrophages, and expand T regulatory cells. Helminth-expressed carbohydrates play critical roles in driving much of this immune cell biasing. Studies on helminth glycans have focused on Lewis X, LDN, LDN-DF, other fucosylated structures, chitin, tyvelose, and trehalose, which interact with host antigen presenting cells (APCs) minimally via C-type lectins and/or Toll-like receptors (TLR). Here, we review recent findings on helminth glycan activation of APCs via C-type lectin/TLRs and introduce the concept that glycosylated helminth molecules require endocytosis to function as immune modulators. Second, we describe unpublished data showing that in vivo glycoconjugates comprising multiple copies of glycans on carriers are directly immune modulatory. Lastly, we discuss the observation that CD14 negatively regulates alternative activation of APCs during helminth infection. We close with a discussion on the use of immune modulatory glycans as vaccine adjuvants and as antiinflammatory therapeutics.
寄生虫偏向宿主 CD4(+) T 辅助 (Th) 细胞向 Th2 反应，驱动巨噬细胞的替代激活，并扩增 T 调节细胞。寄生虫表达的碳水化合物在驱动这种免疫细胞偏向方面起着关键作用。对寄生虫糖的研究主要集中在 Lewis X、LDN、LDN-DF、其他岩藻糖基结构、几丁质、tyvelose 和海藻糖上，这些糖通过 C 型凝集素和/或 Toll 样受体 (TLR) 与宿主抗原呈递细胞 (APC) 最小程度地相互作用。在这里，我们回顾了寄生虫糖激活 APC 通过 C 型凝集素/TLR 的最新发现，并介绍了糖基化寄生虫分子需要内吞作用才能作为免疫调节剂发挥作用的概念。其次，我们描述了未发表的数据，表明体内包含载体上多个糖拷贝的糖缀合物是直接的免疫调节剂。最后，我们讨论了观察到的 CD14 在寄生虫感染过程中负调节 APC 的替代激活的现象。我们以讨论免疫调节糖作为疫苗佐剂和抗炎治疗剂的应用结束。
