Pearce Edward J, Kane Colleen M, Sun Jie
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa., USA.
Chem Immunol Allergy. 2006;90:82-90. doi: 10.1159/000088882.
There is increasing awareness that dendritic cells (DCs) can interpret pathogen-inherent signals and play a pivotal role in polarizing Th cell differentiation. Polarized Th1 responses are induced by DCs, which respond to pathogen-derived TLR ligands to mature and produce IL-12 and related cytokines that are instrumental in Th1 cell outgrowth. In contrast, DCs exposed to SEA (soluble egg Ag from the helminth parasite Schistosoma mansoni) retain a (modified) immature phenotype and induce Th2 responses. In addition to providing positive signals for Th1 cell development, DCs activated to mature by TLR-engagement also provide a potent negative signal that prevents the development of Th2 cells. Production of this signal is dependent upon a MyD88-dependent signaling pathway in DCs. In contrast, exposure of DCs to SEA severely limits their ability to respond to inflammatory TLR ligands such as LPS and CpG. Thus as part of their pathogen-specific response programs, DC can exert negative as well as positive signals for Th response polarization. These effects may have powerful and systemic effects on disease outcome.
人们越来越意识到，树突状细胞（DCs）能够解读病原体固有信号，并在极化Th细胞分化过程中发挥关键作用。DCs诱导极化的Th1反应，其对病原体衍生的TLR配体作出反应而成熟，并产生对Th1细胞生长起重要作用的IL-12及相关细胞因子。相反，暴露于SEA（来自曼氏血吸虫这种蠕虫寄生虫的可溶性虫卵抗原）的DCs保持（一种修饰的）未成熟表型并诱导Th2反应。除了为Th1细胞发育提供正向信号外，通过TLR结合而被激活至成熟的DCs还提供一种有效的负向信号，该信号可阻止Th2细胞的发育。这种信号的产生依赖于DCs中MyD88依赖的信号通路。相反，DCs暴露于SEA会严重限制其对诸如LPS和CpG等炎性TLR配体作出反应的能力。因此，作为其病原体特异性反应程序的一部分，DCs可为Th反应极化施加负向以及正向信号。这些效应可能对疾病结局产生强大的全身性影响。
