ESAT6-induced IFNgamma and CXCL9 can differentiate severity of tuberculosis.

ESAT6-induced IFNgamma and CXCL9 can differentiate severity of tuberculosis.
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DOI:
10.1371/journal.pone.0005158
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Hussain R
Hussain R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hasan Z;Jamil B;Ashraf M;Islam M;Yusuf MS;Khan JA;Hussain R

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针对结核分枝杆菌的保护性反应取决于适当的 T 细胞和巨噬细胞激活。分枝杆菌抗原 6 kDa 早期分泌抗原靶标 (ESAT6) 和培养物滤过蛋白 10 (CFP10) 可以检测结核分枝杆菌特异性 IFNγ 反应。然而,大多数研究是在非流行地区进行的,目的是研究肺结核(PTB)。我们研究了 ESAT6 和 CFP10 在 PTB 和肺外 (EPul) TB 中诱导的细胞因子和趋化因子反应。使用离体全血测定系统测定患有有限疾病(LNTB,n = 24)或严重疾病(SevTB,n = 22)的 PTB(n = 30)和 EPulTB 患者以及健康流行对照(EC)的 IFNγ、IL10、CXCL9 和 CCL2 反应。还确定了对细菌 LPS 的反应。 ESAT6 和 CFP10 诱导的 IFNγ 在 EC 和 TB 患者之间具有可比性。 LNTB 中 ESAT6 和 CFP10 诱导的 IFNγ 分泌量均高于 PTB。与 PTB 相比,EPulTB 中 ESAT6 诱导的 CXCL9 更大,与 LNTB 相比,SevTB 中 ESAT6 诱导的 CXCL9 有所增加。 PTB 患者中 CFP10 诱导的 CCL2 高于 LNTB 患者。与 LNTB 患者相比,LPS 刺激的 CXCL9 在 SevTB 中最强,LPS 诱导的 CCL2 在 PTB 中增加。在所有结核病患者中,ESAT6 诱导的 IFNγ 和 CXCL9 之间存在正相关性,但 IFNγ 和 CCL2 仅在 LNTB 中相关。 ESAT 诱导的 CCL2 和 CXCL9 在 LNTB 中显着相关,而 LPS 反应的相关性仅在 SevTB 中存在。 ESAT6 诱导的 IFNγ 和 CXCL9 可以区分有限和严重的结核感染。
Protective responses against Mycobacterium tuberculosis are dependent on appropriate T cell and macrophage activation. Mycobacterial antigen six kDa early secreted antigenic target (ESAT6) and culture filtrate protein 10 (CFP10) can detect M. tuberculosis specific IFNγ responses. However, most studies have been performed in non-endemic regions and to study pulmonary tuberculosis (PTB). We have studied ESAT6 and CFP10 induced cytokine and chemokines responses in PTB and extrapulmonary (EPul) TB. IFNγ, IL10, CXCL9 and CCL2 responses were determined using an ex vivo whole blood assay system in PTB (n = 30) and EPulTB patients with limited (LNTB, n = 24) or severe (SevTB, n = 22) disease, and in healthy endemic controls (ECs). Responses to bacterial LPS were also determined. ESAT6- and CFP10-induced IFNγ was comparable between ECs and TB patients. Both ESAT6- and CFP10-induced IFNγ secretion was greater in LNTB than PTB. ESAT6-induced CXCL9 was greater in EPulTB as compared with PTB, with an increase in SevTB as compared with LNTB. CFP10-induced CCL2 was higher in PTB than LNTB patients. LPS-stimulated CXCL9 was greatest in SevTB and LPS-induced CCL2 was increased in PTB as compared with LNTB patients. A positive correlation between ESAT6-induced IFNγ and CXCL9 was present in all TB patients, but IFNγ and CCL2 was only correlated in LNTB. ESAT-induced CCL2 and CXCL9 were significantly associated in LNTB while correlation in response to LPS was only present in SevTB. ESAT6 induced IFNγ and CXCL9 can differentiate between limited and severe TB infections.
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