Hasan Zahra, Jamil Bushra, Ashraf Mussarat, Islam Muniba, Yusuf Muhammad S, Khan Javaid A, Hussain Rabia
Department of Pathology and Microbiology, The Aga Khan University, Karachi, Pakistan.
PLoS One. 2009;4(4):e5158. doi: 10.1371/journal.pone.0005158. Epub 2009 Apr 2.
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 IFNgamma 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.
IFNgamma, 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 IFNgamma was comparable between ECs and TB patients. Both ESAT6- and CFP10-induced IFNgamma 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 IFNgamma and CXCL9 was present in all TB patients, but IFNgamma 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 IFNgamma and CXCL9 can differentiate between limited and severe TB infections.
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。结核分枝杆菌抗原6 kDa早期分泌抗原靶标（ESAT6）和培养滤液蛋白10（CFP10）可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，且研究对象为肺结核（PTB）。我们研究了ESAT6和CFP10诱导的细胞因子和趋化因子在PTB和肺外（EPul）结核中的反应。
使用体外全血检测系统测定PTB患者（n = 30）、疾病程度有限的肺外结核患者（LNTB，n = 24）或严重肺外结核患者（SevTB，n = 22）以及健康流行地区对照者（ECs）中IFNγ、IL10、CXCL9和CCL2的反应。还测定了对细菌脂多糖（LPS）的反应。
ECs和结核病患者中ESAT6和CFP10诱导的IFNγ相当。LNTB中ESAT6和CFP10诱导的IFNγ分泌均高于PTB。与PTB相比，ESAT6诱导的CXCL9在EPulTB中更高，与LNTB相比，SevTB中CXCL9增加。CFP10诱导的CCL2在PTB患者中高于LNTB患者。LPS刺激的CXCL9在SevTB中最高，与LNTB患者相比，LPS诱导的CCL2在PTB中增加。所有结核病患者中ESAT6诱导的IFNγ与CXCL9呈正相关，但IFNγ与CCL2仅在LNTB中相关。ESAT诱导的CCL2和CXCL9在LNTB中显著相关，而对LPS反应的相关性仅在SevTB中存在。
ESAT6诱导的IFNγ和CXCL9可区分局限性和严重结核感染。
