The human immune response to tuberculosis and its treatment: a view from the blood.
Bottom Line: 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 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.
Affiliation: TB Centre and Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK.Show MeSH
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Mentions: Evidence to date demonstrates that blood transcriptomics present a robust approach for studying the immune response in tuberculosis and other diseases, as similar findings have now been reported from various groups in different geographical locations. The findings offer information as to the immune response underlying the pathogenesis of tuberculosis and may provide tools toward diagnosis, treatment monitoring, and in the development of host-directed therapy regimens to support drug treatment. The potential use of blood transcriptomics in the clinical management of tuberculosis is likely to support current diagnostic tests and may help to speed up diagnosis and treatment, thus reducing transmission. The development of clinic-friendly tools for supporting the diagnosis of tuberculosis and treatment monitoring have been suggested to rely on a set of discriminant classifiers (consisting of between 12 and 100 genes) that would be easily convertible into a PCR-based affordable assay, allowing its development in the clinic for tuberculosis diagnosis. Meta-analyses of diverse studies on the blood transcriptome of tuberculosis, in the context of other infectious or non-communicable diseases, are required to determine the unifying signature reflecting tuberculosis versus other diseases and the blood signature for tuberculosis treatment success. It is possible with advancing technology and decreasing pricing that a composite whole genome expression profile, obtained using either microarray or in the future RNA-Seq, may be useable rather than discriminant classifiers. This will require the development of sophisticated tools for rapid integration of complex host transcriptional signatures, the clinical data and the pathogen identification, and storage and easy access to such data. Advancement of bioinformatics tools (37) will also help in uncovering biological pathways underlying disease susceptibility, including co-infection, and also help to uncover the comorbidities caused by infectious and non-communicable diseases. This will require iterative research approaches between experimental models and human disease (1, 3, 5, 79) (Fig.7) to establish the function of immune and inflammatory pathways and molecules in resistance or susceptibility to M. tuberculosis infection.
Affiliation: TB Centre and Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK.