Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high evels of Th1 cytokines and the IL-4 antagonist IL-4δ2
Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high evels of Th1 cytokines and the IL-4 antagonist IL-4δ2
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DOI：
10.4049/jimmunol.172.11.6938
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Doherty, TM
中科院分区：
文献类型：
--
作者：
Demissie, A;Abebe, M;Doherty, TM
大多数健康的个体暴露于结核分枝杆菌不会发展疾病和确定什么构成“保护性免疫”是一个圣杯的M。结核免疫学众所周知，IFN-γ对保护是必不可少的，但同样明显的是，IFN-γ水平本身并不能解释免疫/易感性二分法。关于免疫相关性的争议仍然存在，因为识别感染但健康的个体（那些免疫的人）是有问题的。因此，我们使用了M的识别。结核病毒力因子早期分泌抗原靶标6来鉴定来自结核病（TB）流行和非流行地区（埃塞俄比亚和丹麦）的健康但受感染的个体，并将直接离体表达的细胞因子的信号与在TB患者中发现的模式进行了比较。我们发现，结核病患者的特点是降低水平的Th 1细胞因子和IL-10水平的增加与健康的感染和非感染的社区对照。有趣的是，与TB患者或未感染个体相比，健康感染受试者表现出IL-4拮抗剂IL-4 δ 2的选择性增加。这些数据表明，长期控制M。结核病感染不仅与Th 1应答的升高有关，而且与Th 2应答的抑制有关。
The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is essential for protection, but it is also apparent that IFN-gamma levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4delta2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.