title: Increased frequency of myeloid-derived suppressor cells during active tuberculosis and after recent mycobacterium tuberculosis infection suppresses T-cell function.
abstract: BACKGROUND
  Inadequacy of T-cell responses may result in the development of tuberculosis (TB). Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell function in cancer biology and recently in several infectious diseases.
  
  
  OBJECTIVE
  To explore the presence and role of MDSCs in TB.
  
  
  METHODS
  We analyzed surface markers of MDSCs in peripheral blood and at the site of disease in TB cases and in patients with lung cancer, and in peripheral blood of asymptomatic tuberculin skin test-positive individuals with recent (household) or remote exposure to Mycobacterium tuberculosis (M.tb) and in uninfected healthy control subjects. To evaluate the suppressive capacity of MDSCs, cells of household contacts infected with M.tb and TB cases were isolated and cocultured with CD3(+) T cells.
  
  
  RESULTS
  Our results demonstrate an increased presence of MDSCs after recent M.tb infection and disease. We confirm their suppression of CD4(+) T-cell function, including reduced cytokine responses and inhibition of CD4(+) T-cell proliferation. Only MDSCs from TB cases reduced T-cell activation, altered T-cell trafficking, and suppressed CD8(+) T-cell functions. M.tb-expanded MDSCs were associated with significantly higher IL-1β, IL-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1, and reduced granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein-1 beta levels in coculture.
  
  
  CONCLUSIONS
  These data reveal that innate MDSCs are induced not only during active TB at similar levels as found in cancer, but also in healthy individuals after recent exposure to M.tb. These cells diminish protective T-cell responses and may contribute to the inability of hosts to eradicate the infection and add to the subsequent development of TB disease.
authors.affiliation: 1 Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, and.
authors.forename: Nelita
authors.initials: N
authors.lastname: du Plessis
authors.forename: Laurianne
authors.initials: L
authors.lastname: Loebenberg
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kriel
authors.forename: Florian
authors.initials: F
authors.lastname: von Groote-Bidlingmaier
authors.forename: Eliana
authors.initials: E
authors.lastname: Ribechini
authors.forename: Andre G
authors.initials: AG
authors.lastname: Loxton
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008175:Lung Neoplasms / Q000097:blood; D009164:Mycobacterium Infections / Q000097:blood / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test / Q000379:methods; D014376:Tuberculosis / Q000097:blood / Q000276:immunology*
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor