Research ArticleTuberculosis

Immune correlates of tuberculosis disease and risk translate across species

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Science Translational Medicine  29 Jan 2020:
Vol. 12, Issue 528, eaay0233
DOI: 10.1126/scitranslmed.aay0233

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Translating TB

Mycobacterium tuberculosis can cause tuberculosis (TB) disease in humans, although the majority of infected individuals naturally control infection and never show symptoms. To better understand immune control of M. tuberculosis, Ahmed et al. compared gene expression data from infected humans and different animal models. Gene expression differing between disease progression and control identified potentially beneficial shared pathways. Some pathways were followed up by examining M. tuberculosis infection in gene-deficient inbred mice. These results highlight how focusing on commonalities in TB infection can lead to new insights for treating TB.


One quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Although most infected individuals successfully control or clear the infection, some individuals will progress to TB disease. Immune correlates identified using animal models are not always effectively translated to human TB, thus resulting in a slow pace of translational discoveries from animal models to human TB for many platforms including vaccines, therapeutics, biomarkers, and diagnostic discovery. Therefore, it is critical to improve our poor understanding of immune correlates of disease and protection that are shared across animal TB models and human TB. In this study, we have provided an in-depth identification of the conserved and diversified gene/immune pathways in TB models of nonhuman primate and diversity outbred mouse and human TB. Our results show that prominent differentially expressed genes/pathways induced during TB disease progression are conserved in genetically diverse mice, macaques, and humans. In addition, using gene-deficient inbred mouse models, we have addressed the functional role of individual genes comprising the gene signature of disease progression seen in humans with Mtb infection. We show that genes representing specific immune pathways can be protective, detrimental, or redundant in controlling Mtb infection and translate into identifying immune pathways that mediate TB immunopathology in humans. Together, our cross-species findings provide insights into modeling TB disease and the immunological basis of TB disease progression.

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