Small Molecule-directed Immunotherapy against Recurrent Infection by Mycobacterium tuberculosis

• DOI: 10.1074/jbc.m114.558098
• Publication Date: 2014-04-08T00:26:11Z
• Authors: Debapriya Bhattac...; Ved Prakash Dwivedi; Mamoudou Maiga; Mariama Maiga; Luc Van Kaer; William R. Bishai; Gobardhan Das
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Immunology; Mycobacterium tuberculosis; Th1 Cells; Flow Cytometry; 3. Good health; Mice; 03 medical and health sciences; Th2 Cells; Animals; Tuberculosis; Immunotherapy

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