title: Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.
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.
authors.affiliation: 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.
authors.forename: L D
authors.initials: LD
authors.lastname: Tientcheu
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Maertzdorf
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Weiner
authors.affiliation: Disease Control and Elimination Theme, Medical Research Council Unit-The Gambia, Fajara, The Gambia.
authors.forename: I M
authors.initials: IM
authors.lastname: Adetifa
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Mollenkopf
authors.affiliation: Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
authors.forename: J S
authors.initials: JS
authors.lastname: Sutherland
authors.affiliation: Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
authors.forename: S
authors.initials: S
authors.lastname: Donkor
authors.affiliation: Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
authors.forename: B
authors.initials: B
authors.lastname: Kampmann
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: S H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: H M
authors.initials: HM
authors.lastname: Dockrell
authors.affiliation: 1] Vaccinology Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia [2] World Health Organization Regional Office for Africa, Brazzaville, Congo.
authors.forename: M O
authors.initials: MO
authors.lastname: Ota
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D059467:Transcriptome / Q000187:drug effects*; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4