The role of neutrophil granulocytes as target cells and transport vehicle for intracellular pathogens

中性粒细胞作为细胞内病原体的靶细胞和运输工具的作用

• 批准号: 5358069
• 负责人: Professor Dr. Tamás Laskay
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5358069?language=en
• 关键词: role; neutrophil; granulocytes; target; cells

Neutrophil granulocytes (PMN) are recruited rapidly to the skin infected with Leishmania major (L. major) and PMN have been recently shown to facilitate the development of leishmanial disease. We have found that PMN are able to phagocytose Leishmania promastigotes both in vitro and in vivo. Importantly, the parasites delay the spontaneous apoptosis of infected PMN for at least 24-72 h and, as a result, parasites survive intracellularly in PMN. These data suggested that the invasion of PMN is an important early step to establish the leishmanial infection. The aim of the proposed study is to understand the role of PMN in the disease development after infection with intracellular pathogens. The study will investigate the molecular basis of recognition of Leishmania by PMN and the mechanism of pathogeninduced inhibition of PMN apoptosis. Once the anti-apoptotic pathway used by Leishmania is clarified, it will tested whether this is a general mechanism of intracellular pathogens to inhibit PMN apoptosis. In these experiments Chlamydia pneumoniae will be used, a bacterium which we have shown to inhibit PMN apoptosis as well. Experiments are planned to analyse the role of PMN as transport vehicle of Leishmania and Chlamydia contributing to the "silent entry" of the pathogens into monocytes/ macrophages. In order to understand the molecular mechanisms of PMN function in an infection, cDNA microarray analysis will be carried out to identify genes expressed by neutrophils after exposure to intracellular pathogens.

中性粒细胞（PMN）迅速募集到感染了硕大利什曼原虫（L.主要的）和中性粒细胞最近已被证明促进利什曼病的发展。我们发现中性粒细胞在体外和体内都能吞噬利什曼原虫前鞭毛体。重要的是，寄生虫延迟感染的PMN的自发性凋亡至少24-72小时，因此，寄生虫在PMN细胞内存活。这些数据表明，中性粒细胞的入侵是一个重要的早期步骤，建立利什曼原虫感染。本研究的目的是了解PMN在细胞内病原体感染后疾病发展中的作用。本研究旨在探讨利什曼原虫对中性粒细胞识别的分子基础及病原体抑制中性粒细胞凋亡的机制。一旦利什曼原虫所使用的抗凋亡途径被阐明，将测试这是否是胞内病原体抑制PMN凋亡的一般机制。在这些实验中，将使用肺炎衣原体，我们已经证明这种细菌也能抑制PMN凋亡。实验计划分析中性粒细胞作为利什曼原虫和衣原体的运输工具的作用，有助于病原体进入单核细胞/巨噬细胞的“沉默进入”。为了了解感染中PMN功能的分子机制，将进行cDNA微阵列分析以鉴定暴露于细胞内病原体后由中性粒细胞表达的基因。