Immunotherapeutic potential of n-terminally formylated ESAT-6 protein in murine tuberculosis

Abstract

Background: The early secreted antigenic target-6 kDa (ESAT-6) being one of the important antigens expressed by Mycobacterium tuberculosis (MTB) has been widely investigated for its strong immunmodulatory effects. We have previously evaluated the immunotherapeutic efficacy of ESAT-6 in the murine model of experimental tuberculosis (TB). Now in the present study, we have evaluated the immunotherapeutic efficacy of N-terminally formylated form of ESAT-6 (f-ESAT-6) in murine TB. Materials and Methods: The production and purification of f-ESAT-6 have been discussed in our earlier report (Mir SA and Sharma S, 2014). In the present study, the MTB H37Rv-infected mice were treated with f-ESAT-6 alone or in combination with anti-TB drugs (ATDs). Four weeks postinitiation of the treatment, the experimental mice were sacrificed, and the colony-forming units (CFUs) were enumerated in their lungs and spleen as described in “materials and methods” section. Results: The N-terminally formylated ESAT-6 protein (f-ESAT-6) induced a moderate reduction in the bacterial load in the target organs of infected mice. Compared to the dimethyldioctadecyl ammonium bromide treated and untreated groups, the f-ESAT-6 treatment significantly reduced the CFU in the spleen and lungs of infected mice by 0.377 log10 units (P < 0.05) and 0.396 log10 units (P < 0.01), respectively. The administration of f-ESAT-6 in combination with ATDs revealed an additional immunotherapeutic effect and elicited higher therapeutic efficacy over drugs (ATDs) alone. Conclusion: The results of the present study clearly indicate that f-ESAT-6 protein alone as well as in combination with the conventional ATDs induce moderate therapeutic effect against experimental TB.

Keywords

• anti-tuberculosis drugs
• colony-forming unit
• histopathology
• immunotherapy
• n-formylated-early secreted antigenic target-6
• tuberculosis