Immunoregulation /immune Recognition In Filarial/Nonfila

淋巴丝虫病中寄生虫抗原特异性人类T细胞应答的深刻调节的机制已经通过证明涉及的多个途径来解决。通过使用活的寄生虫和寄生虫抗原，我们已经证明，抗原呈递细胞（APC）的功能在疟疾感染中发生了深刻的改变，并且在转录和蛋白质水平上，患者感染的T细胞诱导了共同阻止Th 1型T细胞活化的途径（SOCS基因，泛素连接酶，调节网络）。 此外，细胞凋亡的诱导似乎是一个共同的机制，活丝虫影响宿主的反应，并在TRAIL和caspase 3依赖性mechanisism。 由于下调机制在慢性蠕虫感染中被诱导，我们试图研究这种下调对非寄生虫性反应和疾病的溢出效应。为此，我们正在进行临床试验和体外模型，证明了预先存在的慢性蠕虫感染对分枝杆菌易感性的影响，调节对空气过敏原的反应，并可能对HIV产生影响。 由于许多与丝虫感染相关的病理学与淋巴功能障碍有关，我们建立了一个人体体外模型来研究寄生虫/淋巴细胞的相互作用。通过从血管内皮细胞（BEC）中纯化淋巴管内皮细胞（LEC），我们已经能够证明存在诱导淋巴管生成和异常血管形成的fialrial寄生虫分子。

The mechanisms underlying the profound modulation of parasite antigen-specific human T cell responses in lymphatic filariasis have been addressed by demonstrating the multiple pathways involved. By using live parasites and parasite antigen, we have demonstrated that both antigen presenting cell (APC) function in profoundly altered in fiarial infection and that at both the transcriptional and protein level, the T cells from patients with patent infection have induced pathsways (SOCS genes, ubiquin ligases, regulatory networks) that in concert prevent Th1-type T cell actiation. Moreover, the induction of apoptosis appears to be a common mechanism by which live filarial parasites influences the host response and does so in a TRAIL- and caspase 3-dependent mechansism. Because downregulatory mechanims are induced in chronic helminth infection, we have attempted to study the spillover effect of the this downregulation on responses and diseases that are non-parasitic. To this end, we have both clinical trials underway and in vitro models that have demostrated the influence of pre-existing chronic helminth infection on susceptibility to mycobacteria, on modulating the response to aeroallergens, and potentially to HIV. Because much of the pathology associated with filarial infections is related to lymphatic dysfunction, we have established a human in vitro model to examine parasite/lymphatic cell interaction. By purifying lymphatic endothelial cells (LEC) from blood vascular endothelial cells (BEC), we have been able to demostrate the presence of fialrial parasite molecules that induce lymphangiogenesis and abnormal vasculuar tube formation.