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Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment

Genes & Immunity volume 16, pages 347–355 (2015)Cite this article

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Abstract

The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages.

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Acknowledgements

We thank the Gambian National Leprosy and Tuberculosis Programme for their continuing collaboration. We are also grateful to study participants, field workers, especially K Kanyi and O Ceesay for performing sample collection, MRC TB clinical staff and P Camara for obtaining consent and enrolling participants, TB immunology and TB diagnostic laboratory staff, and M Antonio, P Owiafe, A Bojang, J Mendy, M Daramy, J Otu and F Mendy for laboratory assistance. We also thank T Togun for clinical examination of study patients and ML Grossman for editorial support. Finally, we thank Metabolon Inc. for generating the metabolic profiles. The study was funded by the MRC Unit, The Gambia as a PhD fellowship awarded to LDT, the European Commission Advanced Immunization Technologies (ADITEC) Grant FP7-HEALTH-2011-280873, and the Max Planck Institute for Infection Biology in Berlin, Germany.

Author contributions

MOO, SHEK, LDT, HMD and JM conceived and designed the experiments. HJM, LDT and JM performed laboratory analysis. LDT, JM and JW performed statistical analysis. SD, MOO and IMA collected epidemiology and clinical information. SHEK, BK, JW and MOO contributed reagents/materials/analysis tools. All authors LDT, JM, BK, JSS, HMD, SHEK and MOO wrote the paper.

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Author notes

  1. L D Tientcheu and J Maertzdorf: These authors contributed equally to this work

Authors and Affiliations

  1. Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia

    L D Tientcheu, J S Sutherland, S Donkor, B Kampmann & M O Ota

  2. Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

    L D Tientcheu & H M Dockrell

  3. Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon

    L D Tientcheu

  4. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany

    J Maertzdorf, J Weiner, H-J Mollenkopf & S H E Kaufmann

  5. Disease Control and Elimination Theme, Medical Research Council Unit-The Gambia, Fajara, The Gambia

    I M Adetifa

  6. World Health Organization Regional Office for Africa, Brazzaville, Congo

    M O Ota

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  1. L D Tientcheu
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Correspondence to L D Tientcheu.

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Tientcheu, L., Maertzdorf, J., Weiner, J. et al. Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment. Genes Immun 16, 347–355 (2015). https://doi.org/10.1038/gene.2015.21

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