AUTHOR=Coppola Mariateresa , Lai Rachel P-J. , Wilkinson Robert J. , Ottenhoff Tom H. M. 

TITLE=The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.763364

DOI=10.3389/fimmu.2021.763364

ISSN=1664-3224

ABSTRACT=<p><italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) genes encoding proteins targeted by vaccines and drugs should be expressed in the lung, the main organ affected by <italic>Mtb</italic>, for these to be effective. However, the pulmonary expression of most <italic>Mtb</italic> genes and their proteins remains poorly characterized. The aim of this study is to fill this knowledge gap. We analyzed large scale transcriptomic datasets from specimens of <italic>Mtb</italic>-infected humans, TB-hypersusceptible (C3H/FeJ) and TB-resistant (C57BL/6J) mice and compared data to <italic>in vitro</italic> cultured <italic>Mtb</italic> gene-expression profiles. Results revealed high concordance in the most abundantly <italic>in vivo</italic> expressed genes between pulmonary <italic>Mtb</italic> transcriptomes from different datasets and different species. As expected, this contrasted with a lower correlation found with the highest expressed <italic>Mtb</italic> genes from <italic>in vitro</italic> datasets. Among the most consistently and highly <italic>in vivo</italic> expressed genes, 35 have not yet been explored as targets for vaccination or treatment. More than half of these genes are involved in protein synthesis or metabolic pathways. This first lung-oriented multi-study analysis of the <italic>in vivo</italic> expressed <italic>Mtb</italic>-transcriptome provides essential data that considerably increase our understanding of pulmonary TB infection biology, and identifies novel molecules for target-based TB-vaccine and drug development.</p>