Differential Live Mycobacterium tuberculosis-, M-bovis BCG-, Recombinant ESAT6-, and Culture Filtrate Protein 10-Induced Immunity in Tuberculosis

Zahra Hasan, Aga Khan University
Bushra Jamil, Aga Khan University
Mussarat Ashraf, Aga Khan University
Muniba Islam, Aga Khan University
Maqboola Dojki, Aga Khan University
Muhammad Irfan, Aga Khan University
Rabia Hussain, Aga Khan University


The high prevalence of Mycobacterium tuberculosis makes it imperative that immune responses to evaluate could be predictive of infection. We investigated live Mycobacterium-and recombinant antigen-induced cytokine and chemokine responses in Patients with active tuberculosis (TB) compared with those of healthy controls from an area where TB is endemic (ECs). M. tuberculosis-, M. bovis BCG-, ESAT6-, and culture filtrate protein 10 (CFP10)-induced responses were determined in peripheral blood mononuclear cells from Patients with pulmonary TB (n = 38) and ECs (n = 39). The levels of the cytokines gamma interferon (IFN-gamma) and interleukin-10 (IL-10) and the chemokines CCL2, CCL3, and CXCL9 were measured. The levels of M. tuberculosis-and BCG-induced IFN-gamma secretion were significantly reduced (P = 0.002 and P < 0.01, respectively), while the amount of IL-10 induced by both virulent (P < 0.01) and avirulent (P = 0.002) mycobacteria was increased in Patients with TB. The ESAT6-induced IFN-gamma responses were increased in the Patients with TB (P = 0.013) compared with those in the EC group. When tuberculin skin test (TST)-negative (TST(-), induration, < 10 mm) and TST-positive (TST(-)) donors were studied separately, both TST(-) and TST(+) individuals showed increased IFN-gamma responses to M. tuberculosis compared with the responses of the Patients with TB (P = 0.037 and P = 0.006, respectively). However, only TST(+) ECs showed reduced IFN-gamma responses to ESAT6 (P = 0.008) compared with the responses of the Patients with TB. The levels of M. tuberculosis-induced CCL2 (P = 0.006) and CXCL9 (P = 0.017) were greater in the Patients with TB. The levels of CCL3 secretion in response to Mycobacterium and antigen stimulation were comparable between the two groups. While the levels of ESAT6-induced chemokines did not differ between the Patients with TB and the ECs, the levels of CFP10-induced CCL2 (P = 0.01) and CXCL9 (P = 0.001) were increased in the Patients. These data indicate differential host IFN-gamma, CXCL9, and CCL2 responses to live mycobacteria and mycobacterial antigens and have implications for the identification of potential biomarkers of infection which could be used for the diagnosis of TB.