Researchers Identify Key Protein In Immune Response To Malaria And TB

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Researchers Identify Key Protein In Immune Response To Malaria And TB
研究者确认了疟疾与肺结核病中的关键免疫反应蛋白

Article Date: 03 Apr 2007 - 6:00 PDT
文章日期：2007年4月3日（美国太平洋时间）

An international team of researchers has identified a key protein involved in the immune system's response to malaria, tuberculosis (T and a number of other infectious diseases. The insights suggest possible new therapies to tackle these major global diseases.
一支国际研究小组已经确认了在免疫系统对疟疾、肺结核及其他感染性疾病免疫反应过程中的关键蛋白。研究表明可能存在治疗这些全球主要流行疾病的新疗法。

Professor Luke O'Neill from Trinity College Dublin, Ireland, identified the protein in 2001. The protein, known as Mal, alerts the immune system to respond against invading bacteria. Now, Professor Adrian Hill from the Wellcome Trust Centre for Human Genetics, University of Oxford, UK, has shown that there are two variants of Mal in humans and that the combination of these variants determines how the immune system responds.
爱尔兰都柏林三一学院的Luke O'Neill教授在2001年就已经发现了这些蛋白质。一般认为这些蛋白质是免疫系统对细菌入侵人体发出的警报。现在，英国牛津大学Wellcome Trust人类遗传学研究中心的Adrian Hill教授已经发现人体内存在两种Mal变异蛋白，并且这两种变异蛋白的组合决定了免疫系统的反应方式。

The results of the study, funded by the Wellcome Trust, Science Foundation Ireland, Irish Health Research Board and the Agency for Science, Technology and Research, Singapore, are published in the April edition of Nature Genetics this week.
这项研究成果是由爱尔兰Wellcome Trust科学基金、爱尔兰健康研究委员会和新加坡科技发展局赞助的，已发表在本周出版的《自然－遗传学》四月期刊上。

\"Mal is in effect an alarm system for the immune system,\" explains Professor O'Neill. \"When the body is infected with the malaria parasite or other germs, a set of sensors called 'toll-like receptors' (TLRs) lock onto the intruder. TLRs relay the detection via Mal, which wakes up the immune system to mobilise and defend us.\"
O'Neill教授解释说：“Mal蛋白能够有效对免疫系统发出警报。当人体遭受疟疾、寄生虫或其他细菌感染时，一种被称为Toll样受体的传感蛋白会附着在入侵细菌上。Toll样受体通过Mal蛋白传递识别信息，激发免疫系统保护人体。

However, working with patients in Kenya, the Gambia, Vietnam and the UK, Professor Hill and his team showed that there are two common variants of the protein, one which allows the immune system to work normally, the other resulting in too strong a stimulation. A person will carry a combination of two copies of the protein, one from the mother and one from the father.
然而，通过研究肯尼亚、刚果、越南与英国的病例，Hill教授和他的研究小组发现这种蛋白存在两种变异：一种使得免疫系统正常工作；另一种则产生过于强烈的刺激。人体可同时携带一组分别来自于父亲与母亲的Mal变异蛋白。

\"If you have the overactive type, you are twice as likely to succumb to infection because your immune system goes into overdrive, often leading to severe forms of the disease, in a manner akin to 'friendly fire',\" explains Professor Hill, a Wellcome Trust Principal Research Fellow. \"Similarly, if you have two copies of the less active form, the body does not fight the infection and you get the disease. The optimum situation is to have one copy of each variant, giving a balanced system, sufficient to mount a response, but not overly activating.\"
Hill博士是Wellcome Trust的主要研究伙伴之一，他解释说：“如果你体内有过度兴奋的变异蛋白，你可能感染的几率是常人的两倍。那是因为免疫系统会过度启动，经常会导致人体严重感染疾病，这与“友军开火”情况类似。”

The researchers found that having the overactive Mal doubled the risk of disease, with a four times greater risk of severe malaria in some populations. Malaria and TB account for over five million deaths per year in the developing world, particularly amongst children.
研究者发现过度兴奋型Mal蛋白使得疾病风险成倍增加，而且会使得一些人群感染严重疟疾的风险提高四倍。疟疾和肺结核导致发展中国家超过五百万人的死亡，尤其是儿童。

\"We hope that a drug that modulates the balance of Mal variants might prevent disease in those who are at greater risk,\" says Professor O'Neill. \"Our next step is to work towards developing such drugs.\"
O'Neill博士说：“我们希望有一种药物调节Mal变异蛋白的平衡，这可能会为那些高风险人群提供疾病预防。我们下一步行动就是朝着研究这样的药物前进。”

The research has been welcomed by Dr Mark Walport, Director of the Wellcome Trust, which funds research into diseases of the developing world such as malaria and TB, mainly through its major overseas programmes.
这项研究受到Mark Walport博士的欢迎，他是Wellcome Trust基因的主任。该基金主要通过为海外项目提供资金，资助研究疟疾、肺结核等一些发展中国家流行的疾病。

\"Malaria and TB present a major challenge to the health of people in the developing world,\" says Dr Walport. \"articularly given the recent rise in the number of cases of drug-resistant strains, it is essential that we understand how the immune system responds to infection if we are to develop novel treatments.\"
Walport博士说：“疟疾和肺结核对发展中国家人群的健康构成了巨大挑战，尤其是在近期抗药物变异型疾病数量上升的情况下。如果我们想开发新的疗法，了解免疫系统的感染反应是必要的。”

The researchers also believe that the findings may provide a valuable insight into how dysfunctional immune systems can lead to non-infectious diseases, specifically autoimmune diseases such as type 1 diabetes and rheumatoid arthritis.
研究者们相信这项发现为免疫功能紊乱如何导致非感染性疾病(特定的自体免疫疾病如糖尿病1型和风湿性关节炎等)提供了有价值的认识。