Immunoregulation /immune Recognition In Filarial/nonfila

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，我们使用活寄生虫（感染期幼虫[L3]或微丝虫）以更生理的方式检查宿主和寄生虫之间的相互作用，重点关注那些影响免疫结果的相互作用。首先，利用人类朗格汉斯细胞和微阵列分析，我们已经证明，只要5l3就能深刻地改变朗格汉斯细胞的生理机能。相比之下，相似数量的L3s在更成熟的人类树突状细胞中诱导的基因很少（这与其他寄生虫诱导的情况相反）。此外，L3s对先天免疫通路中的其他细胞（幼稚T细胞、NK细胞、单核细胞）的作用也截然不同，会诱导促炎级联反应和细胞凋亡。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。为了阐明慢性丝虫病/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）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.