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網(wǎng)4月7日報道，全世界有三分之一的人群感染肺結核桿菌,，但是其中只有十分之一的感染者會引發(fā)結核病,。來自美國哈佛大學公共衛(wèi)生學院的Igor Kamnik研究組在4月份的《自然》科學雜志上發(fā)表了他們最新研究成果。研究者從基因上找到了線索,，表明基因可以控制人體對于感染的抵抗能力,，從而解答為什么某些人群感染結核菌后會引發(fā)結核病,，而另一些人群卻不會引發(fā)疾病之謎。
研究表明老鼠體內(nèi)基因通過阻止細菌復制和改變感染應答過程中細胞凋亡的方式來產(chǎn)生免疫功能,。Kamnik和他的同事們分離出一系列DNA基因序列后培養(yǎng)了一只對結核桿菌先天性特別敏感的老鼠,，然后用相應的其它老鼠體內(nèi)對細菌具有天然抵抗力的基因片斷取代這一基因片斷，他們發(fā)現(xiàn)老鼠對于感染的抵抗力隨著DNA片斷的改變而改變,。
研究組發(fā)現(xiàn)名為Ipr1基因在轉移的DNA序列中通過限制結核桿菌的復制來產(chǎn)生免疫力,，同時也可以改變細胞感染后免疫細胞的凋亡方式。在具有抵抗力的大鼠體內(nèi),，巨噬細胞通過一種“細胞自殺”的方式來控制細胞的凋亡,； 但是對感染特別敏感的老鼠，巨噬細胞的凋亡是一個不受控制的過程,，而更加難以控制細菌的擴散,。與老鼠Ipr1基因等同的人類基因被稱為SP110，研究者建議對SP110基因進行試驗,，研究是否使人體對結核菌產(chǎn)生免疫力,。
加拿大McGill大學的Nada Jabado 和Philippe Gros認為此項研究有助于研究新的抗結核菌藥物，因為它不僅為肺結核發(fā)病機理提供了新的研究視點,，同時,，一旦此項研究對人體有效，就可能為藥物治療提供一個新的分子靶向途徑,。
