Toll样受体和树突状细胞：免疫激活传感器——2011年诺贝尔生理学或医学奖简介

Toll最早由德国科学家克里斯汀·纽斯兰芙哈(Christiane Nüsslein Volhard）等于1985年发现，其功能为调控果蝇体节发育。1996年法国斯特拉斯堡国立研究中心的朱尔斯·霍夫曼(Jules Hoffmann）发现Toll基因产物与果蝇感受病原微生物入侵相关，其激活为进行有效防御所必需；1998年美国斯克里普斯研究所布鲁斯·博伊特勒(Bruce Beutler)发现对细菌致病产物脂多糖（lipopolysaccharide, LPS）耐受的小鼠存在一个与果蝇Toll基因非常类似的突变受体基因，并证实这一Toll样受体（Toll like receptor, TLR）就是识别LPS的受体。这些发现表明哺乳动物与果蝇的先天性免疫激活采用类似的分子。他们两位也因发现了激活先天性免疫应答反应的传感器而分享2011年诺贝尔生理学或医学奖一半的奖金，另一半奖金由美国洛克菲勒大学的拉尔夫·斯坦曼(Ralph Steinman)独享。斯坦曼于1973年发现树突状细胞（dendritic cells, DCs），并证实其可激活T细胞，引发获得性免疫应答。进一步研究表明树突状细胞可感受由先天性免疫应答产生的信号并控制T细胞的激活，使免疫系统只对致病微生物产生应答从而避免对自身内源分子进行攻击。这些发现使我们对免疫系统的激活和调控机制有了深入的了解，有助于开发全新的疾病预防和治疗手段。

Toll Like receptors and Dendritic Cells: Sensors for the Activation of Immune Response - A Brief Introduction to the 2011 Nobel Prize in Physiology or Medicine

Toll, a protein involved in the dorsoventral development of fruit flies, was first discovered by the German Scientist Christiane Nüsslein Volhard and his colleagues in 1985. In 1996, Jules Hoffmann at the National Center for Scientific Research in Strasbourg, France, discovered that the product of Toll was involved in the sensing of pathogenic infections in fruit flies, and its activation was necessary for the initiation of effective defense; In 1998, Bruce A. Beutler at the Scripps Research Institute discovered that the lipopolysaccharide(LPS, a microbial pathogenic product) resistant mouse had a mutation in the receptor gene very similar to the Toll in fruit flies, and proved the Toll like receptor was the sensor of LPS. These discoveries showed that mammals and fruit flies adopt the similar molecules to activate innate immunity. Therefore, they shared the half of the 2011 Nobel Prize in Physiology or Medicine for their discoveries concerning the sensors for the activation of innate immunity. Another half of the prize was awarded to Ralph M. Steinman at the Rockefeller University in New York. In 1973, Steinman discovered the Dendritic cells(DCs) and proved that it could activate the T cells and initiate the adaptive immune response. Further studies showed that the DCs could sense the signals arising from the innate immune response and control the T cell activation. This makes it possible for the immune system to react towards pathogenic microorganisms while avoiding attacks on own body's endogenous molecules. These discoveries provide us further insights into the mechanism of activation and regulation of the immune system, and will facilitate the development of novel methods in disease prevention and treatment.