印度科學家日前在新德里的基因工程與生物學(Genetic Engineering abd Biology)會議上,發表感染結核桿菌的病人能長期與細菌共處原因,是因為啟動幹細胞而達到自體平衡的狀態,這項發現也刊登在<美國科學院學報>(PNAS).
世界衛生組織(WHO)公佈,目前全球有1/3人口感染結核桿菌,但只有10%病人會引起肺結核,其餘90%病人處於長期潛伏的狀態.
當結核桿菌入侵時,人體的免疫系統會活化T淋巴球,破壞結核桿菌及其他外來物的入侵,產生發炎作用形成結核組織(granulomas).事實上,身體的間葉幹細胞(MSC)能受到結核菌的感染,而跑至受傷位置,調控T淋巴球的活性.
科學家利用小鼠模式研究結核桿菌感染機制,發現在脾臟和肝臟切片組織可以看到間葉幹細胞的存在.之後在人體的切片組織也受到證實,並且發現只要有結核桿菌存在,就有間葉幹細胞的出現.
間葉幹細胞會釋放NO,作為第二訊息傳遞因子,抑制T淋巴球免疫反應,於結合組織外形成一道保護層,導致身體與結核桿菌達到平衡共存的狀態.換句話說,細菌會利用宿主體內的幹細胞來達到自我保護的機制,這也是科學家第一次發現.
因此未來的藥物研發以間葉幹細胞為標靶,阻礙間葉幹細胞保護結核桿菌的機制,當無法提供細菌生存的微環境時,體內的免疫系統足以摧毀結核桿菌.
Tuberculosis guarded by stem cells
The researchers found that the reason why tuberculosis patients live so long with their disease has to do with the bacterium's own self-protection mechanisms.
Theoretically, the human immune system should be well equipped to handle TB, because human T-cells can learn how to destroy bacteria and other microscopic invaders.
In practice, people who have TB live with the disease for their whole lives, often dying protracted deaths.
A third of the world's population is infected with Mycobacterium tuberculosis.
The researchers found that the reason why the body's immune system rarely learns to cope with TB has to do with stem cells.
Somehow, TB tricks the body into sending its own mesenchymal stem cells (MSC) to infection sites, nullifying the effect of T-cells.
MSC can be seen as 'master stem cells' that can turn into many different types of cell, including bone.
Gobardhan Das, staff scientist at the International Center for Genetic Engineering and Biology in New Delhi, said the bodies of TB sufferers recruited MSC to infection sites, and that the cells eventually made barriers as a result.
After the disease had spread through the bodies of the mice, the researchers extracted lung and spleen tissue.
The researchers also extracted tissue from human patients who had TB.There was MSC at every site where the researchers also found TB.
Das said that the MSC produced nitric oxide (NO), a gas, in order to attack TB, but that the amount of NO produced did not manage to kill all of the bacteria.
The gas is found in abundance in mammalian bodies, where it acts as a signalling pathway.
Das said that the gas also activated T-cells, and that the MSC ultimately worked against both the body and the TB bacteria, establishing an equilibrium between both.
While most people's TB infections are completely asymptomatic and non-contagious, about 10% of all people infected with Mycobacterium tuberculosis will become sick with an active TB infection at some point in their lifetime.
The only way to avoid becoming actively infected is to maintain a consistently strong immune system.
Das said that the MSC involved in tuberculosis infection created a nest-like microenvironment for the bacteria, and that if there were any way to prevent MSC from being actively deployed in the first place, there would be no nest.
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