Immunoregulation /immune Recognition In Filarial/nonfila

丝虫/非丝虫的免疫调节/免疫识别

• 批准号: 6984872
• 负责人: THOMAS B NUTMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6984872
• 关键词: Filarioidae; Langerhans' cell; RNase protection assay; T lymphocyte; blood treatment; cellular immunity; confocal scanning microscopy; cord blood; dendritic cells; filariasis; flow cytometry; genetic susceptibility; helminthic antigen; host organism interaction; human subject; immune response; immunoregulation; laboratory mouse; microarray technology; microorganism immunology; polymerase chain reaction; tissue /cell culture; western blottings

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.

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，我们已经使用活的寄生虫（感染期幼虫[L3]或微丝蚴）以更生理的方式检查宿主和寄生虫之间的相互作用，重点关注影响免疫结果的相互作用。首先，使用人类朗格汉斯细胞和微阵列分析，我们已经证明，少至5 L3可以深刻地改变朗格汉斯细胞的生理。相比之下，相似数量的L3在更成熟的人类树突细胞中诱导非常少的基因（这与其他寄生虫诱导的基因相反）。此外，L3对先天免疫途径中的其他细胞（初始T细胞、NK细胞、单核细胞）的作用是完全不同的，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应答，就会诱导下调机制。为了阐明在慢性丝虫/蠕虫感染中观察到的这种下调的机制，我们已经鉴定了利用CTLA 4以及调节性T细胞（通过IL-10）作为调节抗原特异性免疫应答的那些的途径。