Masood Kiran Iqbal, Hussain Rabia, Rao Nisar, Rottenberg Martin E, Salahuddin Naseem, Irfan Muhammad, Hasan Zahra
The Aga Khan University, P.O. Box 3500, Stadium Road, Karachi 74800, Pakistan.
J Infect Dev Ctries. 2014 Jan 15;8(1):59-66. doi: 10.3855/jidc.3412.
Expression of Suppressor of cytokine signaling (SOCS)-1 molecules is increased in patients with tuberculosis (TB). Early Secreted Antigen Target (ESAT)-6 kDa - induced IFN-γ responses indicate Mycobacterium tuberculosis infection. The effect of ESAT6- stimulation on SOCS1 in the host is not known.
Healthy asymptomatic controls had a negative (n = 16) or a positive ( n = 13) tuberculin skin test (TST). ESAT6-induced IFN-γ responses classified these controls as positive (EC ESAT6 IFN-γ (+), n = 5) or negative (EC ESAT6 IFN-γ (-), n = 24) responders. Patients had pulmonary (n = 21) or extra-pulmonary (n = 30) tuberculosis. Peripheral blood cells were stimulated with ESAT6 and mRNA expression of IFN-γ and SOCS1 was determined.
ESAT6-induced IFN-γ expression was raised in EC ESAT6 IFN-γ (+) as compared with EC ESAT6 IFN-γ (-), p = 0.019. ESAT6-induced SOCS1 mRNA expression was increased in both pulmonary TB and extra-pulmonary TB patients as compared with both EC groups. ESAT6-induced IFN-γ/SOCS1 mRNA expression ratio was decreased in TB patients as compared with both EC groups.
M. tuberculosis infection induces increased ESAT6-induced IFN-γ responses in both latent and active TB. Our data shows down-regulation of IFN-γ / SOCS1 expression to be induced only in active TB cases, distinguishing them from healthy individuals likely to have latent TB. A decreasing IFN-γ /SOCS1 ratio may leads to reduced Th1 immunity which contributes to inability of the host to control clinical disease.
细胞因子信号转导抑制因子（SOCS）-1分子在结核病（TB）患者中表达增加。早期分泌抗原靶标（ESAT）-6 kDa诱导的IFN-γ反应表明结核分枝杆菌感染。ESAT6刺激对宿主宿主中SOCS1的影响尚不清楚。
健康无症状对照者结核菌素皮肤试验（TST）结果为阴性（n = 16）或阳性（n = 13）。ESAT6诱导的IFN-γ反应将这些对照者分为阳性（EC ESAT6 IFN-γ（+），n = 5）或阴性（EC ESAT6 IFN-γ（-），n = 24）反应者。患者患有肺结核（n = 21）或肺外结核（n = 30）。用ESAT6刺激外周血细胞，并测定IFN-γ和SOCS1的mRNA表达。
与EC ESAT6 IFN-γ（-）相比，EC ESAT6 IFN-γ（+）中ESAT6诱导的IFN-γ表达升高，p = 0.019。与两个EC组相比，肺结核和肺外结核患者中ESAT6诱导的SOCS1 mRNA表达均增加。与两个EC组相比，TB患者中ESAT6诱导的IFN-γ/SOCS1 mRNA表达比值降低。
结核分枝杆菌感染在潜伏性和活动性结核病中均诱导ESAT6诱导的IFN-γ反应增加。我们的数据表明，仅在活动性结核病例中诱导IFN-γ/SOCS1表达下调，这将它们与可能患有潜伏性结核的健康个体区分开来。IFN-γ/SOCS1比值降低可能导致Th1免疫降低，这导致宿主无法控制临床疾病。
