Systems Approach to Understand the Immune Response in Tuberculosis: An Iterative Process between Mouse Models and Human Disease

Tuberculosis remains a disease of considerable mortality and morbidity. The immune response determining whether individuals infected with the pathogen Mycobacterium tuberculosis control the infection, and remain latent, or go on to develop active tuberculosis disease is poorly understood. Our studies used microarray technology to derive blood transcriptional profiles of the host response during tuberculosis, which, combined with data from experimental systems, highlighted a potentially detrimental role for Type I interferons during infection, with important implications for vaccine and therapeutic development. Our studies have also provided candidate biomarkers, which may advance diagnosis and treatment monitoring. These studies thus exemplify the promise of a systems biology approach to understand the immune response to complex infectious disease such as tuberculosis, leading to improved experimental models and systems for improving our mechanistic understanding of why some individuals control the infection whereas others go on to develop active disease.