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Genes Immun. 2015 Jul-Aug;16(5):347-55. doi: 10.1038/gene.2015.21. Epub 2015 Jun 4.

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

Author information

1
1] Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia [2] Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK [3] Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon.
2
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
3
Disease Control and Elimination Theme, Medical Research Council Unit-The Gambia, Fajara, The Gambia.
4
Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
5
Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
6
1] Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia [2] World Health Organization Regional Office for Africa, Brazzaville, Congo.

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.

PMID:
26043170
PMCID:
PMC4515549
DOI:
10.1038/gene.2015.21
[Indexed for MEDLINE]
Free PMC Article

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