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