A major limitation in the development and testing of new tuberculosis (TB) vaccines is the current inadequate understanding of the nature of the immune response required for protection against either infection with Mycobacterium tuberculosis (MTB) or progression to disease. Genome wide RNA expression analysis has provided a new tool with which to study the inflammatory and immunological response to mycobacteria. To explore how currently available transcriptomic data might be used to understand the basis of protective immunity to MTB, we analysed and reviewed published RNA expression studies to (1) identify a “susceptible” immune response in patients with acquired defects in the interferon gamma pathway; (2) identify the “failing” transcriptomic response in patients with TB as compared with latent TB infection (LTBI); and (3) identify elements of the “protective” response in healthy latently infected and healthy uninfected individuals.
Abbreviations

TB, tuberculosis; MTB, Mycobacterium tuberculosis; IFN-γ, interferon-gamma; PBMC, peripheral blood mononuclear cells; MSMD, Mendelian susceptibility to mycobacterial disease; BCG, bacille Calmette–Guerin; LTBI, latent tuberculosis infection

Keywords

Transcriptomics; RNA expression profiling; Tuberculosis; Vaccines; Interferon-γ; Type I interferon