The immune response upon
infection with the pathogen Mycobacterium tuberculosis is poorly understood, hampering the discovery of new treatments and the improvements in diagnosis. In the last years, a blood transcriptional signature in
tuberculosis has provided knowledge on the immune response occurring during active
tuberculosis disease. This signature was absent in the majority of asymptomatic individuals who are latently infected with M.
tuberculosis (referred to as latent). Using modular and pathway analyses of the complex data has shown, now in multiple studies, that the signature of active
tuberculosis is dominated by overexpression of
interferon-inducible genes (consisting of both type I and
type II interferon signaling), myeloid genes, and inflammatory genes. There is also downregulation of genes encoding B and T-cell function. The blood signature of
tuberculosis correlates with the extent of radiographic disease and is diminished upon effective treatment suggesting the possibility of new improved strategies to support diagnostic assays and methods for
drug treatment monitoring. The signature suggested a previously under-appreciated role for
type I interferons in development of active
tuberculosis disease, and numerous mechanisms have now been uncovered to explain how
type I interferon impedes the protective response to M.
tuberculosis infection.