title: Mycobacterium tuberculosis-specific CD4+ T-cell response is increased, and Treg cells decreased, in anthelmintic-treated patients with latent TB.
abstract: In many settings, adults with active or latent tuberculosis will also be coinfected with helminths. Our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity, in a setting where helminth reinfection should not occur. We investigated the potential impact of helminth infection on immune responses to Mycobacterium tuberculosis (Mtb) in patients with latent Mtb infection with or without helminth infection (Strongyloides or Schistosoma), and tested T-cell responses before and after anthelmintic treatment. The study was performed in migrants resident in the United Kingdom, where reexposure and reinfection following anthelmintic treatment would not occur. The frequency of CD4(+) IFN-γ(+) T cells was measured following stimulation with Mtb Purified Protein Derivative or ESAT-6/CFP-10 antigen, and concentrations of IFN-γ in culture supernatants measured by ELISA and multiplex bead array. Helminth infection was associated with a lower frequency of CD4(+) IFN-γ(+) T cells, which increased following treatment. Patients with helminth infection showed a significant increase in CD4(+) FoxP3(+) T cells (Treg) compared to those without helminth infection. There was a decrease in the frequency of Treg cells, and an associated increase in CD4(+) IFN-γ(+) T cells after the anthelmintic treatment. Here, we show a potential role of Treg cells in reducing the frequency and function of antimycobacterial CD4(+) IFN-γ(+) T cells, and that these effects are reversed after anthelmintic treatment.
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Frederic
authors.initials: F
authors.lastname: Toulza
authors.affiliation: Hospital for Tropical Diseases, University College Hospital, and Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Lillian
authors.initials: L
authors.lastname: Tsang
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, UK.|Hospital for Tropical Diseases, University College Hospital, and Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
mesh_terms: D000328:Adult; D000871:Anthelmintics / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D055985:Latent Tuberculosis / Q000150:complications / Q000276:immunology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012552:Schistosomiasis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D013322:Strongyloidiasis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology; D006113:United Kingdom
chemical_list: D000871:Anthelmintics; D014373:Tuberculin; D007371:Interferon-gamma
keywords: Anthelmintic treatment; Helminth infection; IFN-γ; Latent TB infection; Mycobacterium tuberculosis; Regulatory T (Treg) cells