The 6-kilodalton early secreted antigenic target-responsive, asymptomatic contacts of tuberculosis patients express elevated levels of interleukin-4 and reduced levels of gamma interferon
The 6-kilodalton early secreted antigenic target-responsive, asymptomatic contacts of tuberculosis patients express elevated levels of interleukin-4 and reduced levels of gamma interferon
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DOI：
10.1128/iai.74.5.2817-2822.2006
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Doherty, TM
中科院分区：
文献类型：
--
作者：
Demissie, A;Wassie, L;Doherty, TM
众所周知，大多数接触结核分枝杆菌的健康人不会出现临床疾病。我们之前已经证明，在最近接触到的结核病(TB)患者的健康接触者中，对结核分枝杆菌6-kDa早期分泌抗原靶点(ESAT-6)毒力因子的强烈免疫反应与后续疾病的更高风险相关，尽管当时机制尚不清楚。最近有报道称，接触结核分枝杆菌的医护人员中白介素4(IL-4)的高表达也与其随后发病的更高风险相关，受此启发，我们检测了来自埃塞俄比亚的结核病患者的健康家庭接触者中白介素4(IL-4)、其竞争性拮抗剂IL-482和γ-干扰素(干扰素-γ)的表达。然后，我们比较了细胞因子的表达与他们对ESAT-6的识别(ESAT-6在很大程度上仅限于结核病复合体的成员，并作为感染的可靠标志)或Ag85A(一种在分枝杆菌中保守的抗原，用作非特异性对照)。我们的研究表明，在这些最近接触到ESAT-6的人中，对ESAT-6的强烈反应与IL-4的表达升高之间存在相关性。此外，IL-4的高表达与其拮抗剪接变异体IL-482和Th1细胞因子干扰素-γ的低表达有关，这表明在这些高危个体中，甚至在临床症状发展之前，免疫就偏离了保护性的Th1反应。
It is well known that the majority of healthy individuals exposed to Mycobacterium tuberculosis do not become clinically ill. We have previously shown that in recently exposed healthy contacts of tuberculosis (TB) patients, a strong immune response to the M. tuberculosis 6-kDa early secreted antigenic target (ESAT-6) virulence factor correlated with a higher risk of subsequent disease, although the mechanism was unclear at that time. Inspired by recent reports that elevated expression of interleukin-4 (IL-4) in health care workers exposed to M. tuberculosis also correlated with a higher risk of their subsequently developing disease, we examined expression of IL-4, its competitive antagonist IL-482, and gamma interferon (IFN-gamma) in healthy household contacts of TB patients from Ethiopia. We then compared cytokine expression to their recognition of ESAT-6 (which is largely restricted to members of the tuberculosis complex and which serves as a reliable marker of infection) or to Ag85A (an antigen that is conserved among the mycobacteria and serves as a nonspecific control). Our study shows that in these recently exposed individuals, there is a correlation between a strong response to ESAT-6 and elevated expression of IL-4. Further, elevated expression of IL-4 is associated with lower expression of its antagonistic splice variant IL-482 and with the Th1 cytokine IFN-gamma, suggesting that in these at-risk individuals, immunity is skewed away from a protective Th1 response, even before the development of clinical symptoms.