A magnified image of Tuberculosis
Tuberculosis immunity gene found in mice
Catherine Brahic
7 April 2005
Source: SciDev.Net
Researchers have identified a genetic clue as to why some people are immune to the tuberculosis bacterium whereas others develop the disease.
Their findings suggest that a mouse gene — of which humans have a version — confers immunity by stopping the bacterium from replicating and by altering the way cells die in response to infection.
The team, led by Igor Kamnik of the US-based Harvard School of Public Health, published their results in this week's issue of Nature.
One-third of the global population is infected with Mycobacterium tuberculosis, but only one in ten of those infected develop tuberculosis. The difference suggests that genetic factors could control a person's ability to resist the infection.
Kamnik and his colleagues had previously identified a section of DNA that made a strain of inbred mice particularly susceptible to infection by M. tuberculosis.
In their latest research, they replaced this segment with the corresponding one from mice that are naturally resistant to the bacterium. They found that the ability to resist infection was transferred with the segment of DNA.
The team found that a gene called Ipr1 found in the transferred DNA conferred resistance by limiting the replication of M. tuberculosis. The gene also appeared to change the way in which cells of the immune system died as a result of infection.
In the resistant mice, these cells, known as macrophages, died by a form of 'cell suicide' that the body uses to control cell death.
In mice that were susceptible to infection, however, macrophages died by an uncontrolled process that could make it more difficult to control the spread of the bacteria.
The human equivalent of the mouse Ipr1 gene is called SP110. The researchers suggest testing SP110 to see if it conveys resistance to the tuberculosis bacterium in humans.
In an accompanying commentary in Nature, Nada Jabado and Philippe Gros, of McGill University in Canada, say the results could help design new tuberculosis drugs.
"These studies not only provide insight into a novel aspect of TB [tuberculosis] pathogenesis, but, if validated in humans, may reveal new molecular targets for drug treatments," they write.
Scidev.net网4月7日报道，全世界有三分之一的人群感染肺结核杆菌，但是其中只有十分之一的感染者会引发结核病。来自美国哈佛大学公共卫生学院的Igor Kamnik研究组在4月份的《自然》科学杂志上发表了他们最新研究成果。研究者从基因上找到了线索，表明基因可以控制人体对于感染的抵抗能力，从而解答为什么某些人群感染结核菌后会引发结核病，而另一些人群却不会引发疾病之谜。
研究表明老鼠体内基因通过阻止细菌复制和改变感染应答过程中细胞凋亡的方式来产生免疫功能。Kamnik和他的同事们分离出一系列DNA基因序列后培养了一只对结核杆菌先天性特别敏感的老鼠，然后用相应的其它老鼠体内对细菌具有天然抵抗力的基因片断取代这一基因片断，他们发现老鼠对于感染的抵抗力随着DNA片断的改变而改变。
研究组发现名为Ipr1基因在转移的DNA序列中通过限制结核杆菌的复制来产生免疫力，同时也可以改变细胞感染后免疫细胞的凋亡方式。在具有抵抗力的大鼠体内，巨噬细胞通过一种“细胞自杀”的方式来控制细胞的凋亡； 但是对感染特别敏感的老鼠，巨噬细胞的凋亡是一个不受控制的过程，而更加难以控制细菌的扩散。与老鼠Ipr1基因等同的人类基因被称为SP110，研究者建议对SP110基因进行试验，研究是否使人体对结核菌产生免疫力。
加拿大McGill大学的Nada Jabado 和Philippe Gros认为此项研究有助于研究新的抗结核菌药物，因为它不仅为肺结核发病机理提供了新的研究视点，同时，一旦此项研究对人体有效，就可能为药物治疗提供一个新的分子靶向途径。
