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: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=475599
• 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性原虫，可导致以血性痢疾和肝脓肿为特征的阿米巴病。世界上约1%的人口携带这种寄生虫，每年导致5000万例侵袭性疾病和10万人死亡。它是全球十大主要死亡原因之一。目前，这些寄生虫在感染期间没有得到控制的原因尚不清楚。然而，药物治愈的患者对再次侵袭具有抵抗力，这表明发生了保护性免疫。临床和实验研究表明，巨噬细胞(杀死寄生虫的白细胞)介导的细胞免疫在控制和抵抗再次感染方面非常重要。因此，控制阿米巴病的当务之急是开发安全有效的疫苗。寄生虫表面参与疾病起始的主要分子是半乳糖结合蛋白，称为半乳糖凝集素。这种蛋白是免疫显性的，并被患有/患有这种疾病的患者的血清识别。用半乳糖凝集素免疫动物可以保护它们免受挑战感染，这表明它是预防阿米巴病的很好的候选疫苗分子。然而，目前还不知道半乳糖凝集素的哪一部分(S)能引起保护性免疫反应。我们假设，半乳糖凝集素的特定部分可以刺激细胞免疫，从而使宿主防御疾病。因此，本研究的具体目的是：(1)确定半乳糖凝集素刺激天然免疫和获得性免疫反应的关键区域；(2)确定参与保护性免疫的宿主细胞受体和信号事件。我们的策略是首先使用一组识别不同区域的单抗精细绘制半乳糖凝集素的保护性表位图。其次，我们将利用半乳糖凝集素的假定受体(S)缺乏的细胞和动物来鉴定树突状细胞上刺激保护性免疫反应的受体。确定刺激正确的免疫反应所涉及的受体和信号事件的特征对于制定策略以加强针对这种毁灭性疾病的疫苗开发非常重要。