The CFP-10/ESAT-6 complex of Mycobacterium tuberculosis potentiates the activation of murine macrophages involvement of IFN-gamma signaling

Abstract

Secretory antigen of Mycobacterium tuberculosis, culture filtered protein 10(CFP-10) and early secreted antigenic target 6 kDa protein (ESAT-6) are closely correlated with immunogenicity and virulence of Mycobacterium tuberculosis. But the mechanism of its immunogenicity and virulence is still unclear. In this study, we investigated the influence of the CFP-10/ESAT-6 complex on production of IL-12 and nitric oxide (NO) produced by the ANA-1 macrophage cell line. Preincubation with the complex in a time-dependent manner significantly enhanced production of NO and IL-12 released from ANA-1 cells following IFN-gamma stimulation. In addition, the complex up-modulated expression level of IFN-gammaR1 on surface of the macrophages. Furthermore, the effect of the complex on production of IL-12 and NO in ANA-1 cells was suppressed by AG490, a selective inhibitor of JAK/STAT pathway. These data suggest that in the presence of IFN-gamma, CFP-10/ESAT-6 complex represents a new immunogenicity and protective factor that may be, at least partly, due to up modulation of IFN-gammaR1 expression and activation of JAK/STAT pathway.