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

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Abstract
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-γ) and interleukin-10 (IL-10) and the chemokines CCL2, CCL3, and CXCL9 were measured. The levels of M. tuberculosis - and BCG-induced IFN-γ 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-γ 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, + ) donors were studied separately, both TST − and TST + individuals showed increased IFN-γ 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-γ 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-γ, 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.

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