The gal-lectin in host defence against entamoeba histolytica

半乳糖凝集素在宿主防御溶组织内阿米巴中的作用

• 批准号: 121785-2008
• 负责人: Chadee, Khrisendath
• 金额: $ 2.84万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498154
• 关键词: gal; lectin; host; defence; against

Entamoeba histolytica is a parasitic protozoan that causes the disease amebiasis characterized by bloody dysentery and liver abscess. About 1% of the world's population carries the parasite, resulting in 50 million cases of invasive disease and 100,000 deaths per year. It is among the 10 leading causes of mortality worldwide. At present, it is not known why the parasites are not controlled during infection. However, patients who are drug-cured are resistant to reinvasion suggesting that protective immunity occurs. Clinical and experimental studies indicate that cell-mediated immunity mediated by macrophages (the white blood cells that kill the parasites) is important in control and resistance to re-infection. Thus, a priority to the control of amebiasis is to develop a safe and effective vaccine. The major surface molecule on the parasite involved in the initiation of disease is the galactose-binding protein called the Gal-lectin. This protein is immunodominant and is recognized by serum from patients who had/has the disease. Immunization of animals with the Gal-lectin protected them against a challenge infection suggesting it is a good vaccine candidate molecule against amebiasis. However, it is not known what portion(s) of the Gal-lectin elicits the protective immune response. We hypothesized that specific portions of the Gal-lectin stimulates cell-mediated immunity for host defense against the disease. Accordingly, the specific aims of this study are: (1) to identify the critical regions of the Gal-lectin that stimulate innate and adaptive immune responses and, (2) to identify the host cell receptor and the signaling events involved in protective immunity. Our strategy is to first fine map the protective epitopes of the Gal-lectin using a panel of monoclonal antibodies that recognize distinct domains. Secondly, we will identify the receptors on dendritic cells that stimulate a protective immune response by using cells and animals that are deficient in the putative receptor(s) for the Gal-lectin. Characterizing the receptor and the signaling events involved in stimulating the right immune response is important in developing strategies to enhance vaccine development against this devastating disease.

溶组织内阿米巴是一种寄生原虫，引起以血性痢疾和肝脓肿为特征的阿米巴病。 世界上大约1%的人口携带这种寄生虫，每年导致5000万例侵入性疾病和10万例死亡。 它是全世界十大死亡原因之一。 目前，尚不清楚为什么寄生虫在感染过程中没有得到控制。 然而，药物治愈的患者对复发有抵抗力，这表明保护性免疫发生了。 临床和实验研究表明，由巨噬细胞（杀死寄生虫的白色血细胞）介导的细胞介导的免疫在控制和抵抗再感染方面很重要。 因此，研制安全有效的疫苗是控制阿米巴病的当务之急。 寄生虫上参与疾病起始的主要表面分子是称为半乳糖凝集素的半乳糖结合蛋白。 这种蛋白质是免疫显性的，并且被患有该疾病的患者的血清识别。 用半乳糖凝集素免疫动物保护它们免受攻击感染，表明它是对抗阿米巴病的良好疫苗候选分子。 然而，尚不清楚Gal-凝集素的哪一部分引起保护性免疫应答。 我们推测，特定部分的半乳糖凝集素刺激细胞介导的免疫宿主防御疾病。 因此，本研究的具体目的是：（1）鉴定刺激先天性和适应性免疫应答的半乳糖凝集素的关键区域，以及（2）鉴定保护性免疫中涉及的宿主细胞受体和信号传导事件。 我们的策略是首先使用一组识别不同结构域的单克隆抗体来精细绘制半乳糖凝集素的保护性表位。 其次，我们将通过使用缺乏半乳糖凝集素假定受体的细胞和动物来鉴定树突状细胞上刺激保护性免疫应答的受体。 表征参与刺激正确免疫反应的受体和信号传导事件对于开发策略以增强针对这种毁灭性疾病的疫苗开发非常重要。