Immunogenetic and Immunotherapy in Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTb). TB causes mortality of millions of people every year. Mycobacterium bovis Bacillus Calmette Güerin (BCG) is the only officially approved vaccine that protects against miliary TB and children but fails to protect in adulthood presumably because of the lack of long lasting immunological memory. The problem is even more aggravated because of the emergence of multidrug-resistant strains. Therefore, immunogenetics and immunotherapy of antimycobacterial immunity are complex and poorly characterized. However, several studies either in the mouse model or in vitro, using derived dendritic or macrophages derived from PBMCs or human cell lines, have shown that Th1 type cellular immune response represented by IFN-γ, IL-12 in conjunction with IL-17, and IL-23 are key players of the immune protection to M. tuberculosis. It is known that under different settings type I IFNs promote bacterial virulence and disease exacerbation, since a study with active TB patients was concomitant with a dominant neutrophil-driven interferon inducible gene pattern. Furthermore, in an independent cohort of TB patients, ex vivo experiments with BMDCs (bone marrow–derived dendritic cells) and myeloid from lung showed that there is a cross action between the components of IL-1β, eicosanoid pathways (prostaglandin, lipoxins, and leukotrienes) in active TB, while excessive type I IFNs and IL10 induction, concomitant with an inhibition of iNO3 and prostaglandin, could be found. These responses could be used as a therapeutic target instead of any other treatment based on antibiotics. Furthermore, the work from us has demonstrated that interferon alpha plus BCG vaccine protects against mycobacterial infections through modulating the Th1-type cellular immune response, iNOs, and IL-1β production. These immunomodulatory properties of interferon alpha could influence the outcome of the innate and acquired host immune responses in tuberculosis