Immunoregulation /immune Recognition In Filarial/nonfila

在已经证明寄生虫抗原深刻地改变了人类树突状细胞的成熟和功能之后，我们使用活的寄生虫(感染期幼虫[L3]或微丝虫)以更生理学的方式检查宿主和寄生虫之间的相互作用，重点关注影响免疫结果的那些相互作用。首先，利用人类朗格汉斯细胞和微阵列分析，我们已经证明了仅5个L3就可以深刻地改变朗格汉斯细胞的生理。相比之下，在更成熟的人类树突状细胞中，类似数量的L3诱导的基因非常少(这与其他寄生虫诱导的基因相反)。此外，L3s对先天免疫途径中的其他细胞(幼稚T细胞、NK细胞、单核细胞)的作用也有很大的不同，诱导了促炎反应和细胞凋亡。诱导细胞凋亡似乎是丝虫影响宿主反应的一种常见机制。一旦建立了对寄生虫感染的免疫反应，就会诱导下调机制。为了阐明慢性丝虫/蠕虫感染中这种下调的机制，我们已经确定了利用CTLA4和调节性T细胞(通过IL-10)作为调节抗原特异性免疫反应的途径。

Having already demostrated that parasite antigen profoundly alters the maturation and function of human dendritic cells, we have used live parasites (infective stage larvae [L3] or microfilariae) to examine, in a more physiological manner, the interaction between host and the parasite focussing in on those interactions that affect immunological outcome. First, using human Langerhans cells and microarray analysis, we have demonstrated that as few as 5 L3 can profoundly alter Langerhans' cell physiology. In contrast, similar numbers of L3s induce very few genes in more mature human dendritic cells (this in contrast to that induced by other parasites). Moreover, the L3s' effect on other cells in the innate immune pathway (naive T cells, NK cells, monocytes) are profoundly different, with the induction of proinflammatory cascades and apoptosis. The induction of apoptosis appears to be a common mechanism by which the filarial parasites influences the host response. Once the immune response to the parasitic infection is established, downregulatory mechanims are induced. The elucidate the mehansims underlying this downregulation seen in chronic filarial/helminth infection, we have identified pathways that utilize CTLA4 as well as regulatory T cells (through IL-10) as those that modulate the antigen-specific immune response.