Small molecule-directed immunotherapy against recurrent infection by Mycobacterium tuberculosis [Cell Biology]

April 7th, 2014 by Bhattacharya, D., Dwivedi, V. P., Maiga, M., , Kaer, L. V., Bishai, W. R., Das, G.

Tuberculosis (TB) remains the biggest infectious threat to humanity with one third of the population infected, and 1.4 million deaths and 8.7 million new cases annually. Current TB therapy is lengthy and consists of multiple antimicrobials, which causes poor compliance and high treatment dropout, resulting in the development of drug-resistant variants of TB. Therefore, alternate methods to treat TB are urgently needed. Mycobacterium tuberculosis (M. tb) evades host immune responses by inducing T helper (Th) 2 and regulatory T (Treg) cell responses, which diminish protective Th1 responses. Here we show that animals (Stat-6-/-CD4-TGF-betaRIIDN mice) that are unable to generate both Th2 cells and Tregs are highly resistant to M. tb infection. Furthermore, simultaneous inhibition of these two subsets of Th cells by therapeutic compounds dramatically reduced bacterial burden in different organs. This treatment was associated with the generation of protective Th1 immune responses. As these therapeutic agents are not directed to the harboured organisms, they should avoid the risk of promoting the development of drug-resistant M. tb variants.