Science and Research

Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNgamma(pos) T cells and particularly regulatory T cells (Tregs). This was accompanied by significantly reduced mycobacterial loads in the lungs of mice. Importantly, diphtheria toxin-induced depletion of Tregs did not influence mycobacterial loads, but accentuated immunopathology in AdGM-CSF-exposed mice infected with M. bovis BCG. Together, the data demonstrate that AdGM-CSF therapy improves lung protective immunity against M. bovis BCG infection in mice independent of co-recruited Tregs, which however critically contribute to limit lung immunopathology in BCG-infected mice. These data may be relevant to the development of immunomodulatory strategies to limit immunopathology-based lung injury in tuberculosis in humans.

  • Singpiel, A.; Kramer, J.; Maus, R.; Stolper, J.; Bittersohl, L. F.; Gauldie, J.; Kolb, M.; Welte, T.; Sparwasser, T.; Maus, U. A.

Keywords

  • FoxP3
  • Gm-csf
  • Regulatory T cells
  • Tuberculosis
Publication details
DOI: 10.1016/j.imbio.2017.10.042
Journal: Immunobiology
Work Type: Original
Location: BREATH
Disease Area: PALI
Partner / Member: MHH
Access-Number: 29089144

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