TY - JOUR
T1 - ESAT6-induced IFNγ and CXCL9 can differentiate severity of tuberculosis
AU - Hasan, Zahra
AU - Jamil, Bushra
AU - Ashraf, Mussarat
AU - Islam, Muniba
AU - Yusuf, Muhammad S.
AU - Khan, Javaid A.
AU - Hussain, Rabia
N1 - Funding Information:
Recombinant antigens ESAT6 and CFP10 were provided through the TB Vaccine Testing and Research Materials Contract, NIH, NIAID NO1-A1-40091, awarded to Colorado State University, USA.
PY - 2009/4/2
Y1 - 2009/4/2
N2 - Background: 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. Methodology: 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. Principal Findings: 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. Conclusions: ESAT6 induced IFNγ and CXCL9 can differentiate between limited and severe TB infections.
AB - Background: 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. Methodology: 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. Principal Findings: 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. Conclusions: ESAT6 induced IFNγ and CXCL9 can differentiate between limited and severe TB infections.
UR - http://www.scopus.com/inward/record.url?scp=64549121136&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0005158
DO - 10.1371/journal.pone.0005158
M3 - Article
C2 - 19340290
AN - SCOPUS:64549121136
SN - 1932-6203
VL - 4
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e5158
ER -
