title: Host Immune Responses Differ between M. africanum- and M. tuberculosis-Infected Patients following Standard Anti-tuberculosis Treatment.
abstract: Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1α were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-γ and TNF-α production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility.
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.|Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.|Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon.
authors.forename: Leopold D
authors.initials: LD
authors.lastname: Tientcheu
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariëlle C
authors.initials: MC
authors.lastname: Haks
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.|Department of Medical Statistics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Schadrac C
authors.initials: SC
authors.lastname: Agbla
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Sutherland
authors.affiliation: Disease Control and Elimination Theme, Medical Research Council Unit, The Gambia, Fajara, The Gambia.|Department of Infectious Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Ifedayo M
authors.initials: IM
authors.lastname: Adetifa
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
authors.forename: Simon
authors.initials: S
authors.lastname: Donkor
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Quinten
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Daramy
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.|Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.|Microbiology and Infection Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Antonio
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
authors.affiliation: Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, Banjul, The Gambia.|World Health Organization Regional Office for Africa, Brazzaville, Congo.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Ota
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D005714:Gambia; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D014376:Tuberculosis / Q000188:drug therapy* / Q000208:ethnology / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D015415:Biomarkers; D016207:Cytokines; C525005:ESAT-6 antigen, Mycobacterium leprae; C508599:IL5 protein, human; D015848:Interleukin-5; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma