Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Bittersohl, Lara Friederike
Maus, Ulrich A
MetadataShow full item record
AbstractGranulocyte 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 IFNγpos 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.
CitationAdenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells. 2017 Immunobiology
AffiliationTWINCORE; Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Enhanced immunogenicity of BCG vaccine by using a viral-based GM-CSF transgene adjuvant formulation.
- Authors: Wang J, Zganiacz A, Xing Z
- Issue date: 2002 Jul 26
- Transgenic expression of granulocyte-macrophage colony-stimulating factor induces the differentiation and activation of a novel dendritic cell population in the lung.
- Authors: Wang J, Snider DP, Hewlett BR, Lukacs NW, Gauldie J, Liang H, Xing Z
- Issue date: 2000 Apr 1
- Granulocyte-macrophage colony stimulating factor-mediated innate responses in tuberculosis.
- Authors: Szeliga J, Daniel DS, Yang CH, Sever-Chroneos Z, Jagannath C, Chroneos ZC
- Issue date: 2008 Jan
- Improved protection against disseminated tuberculosis by Mycobacterium bovis bacillus Calmette-Guerin secreting murine GM-CSF is associated with expansion and activation of APCs.
- Authors: Ryan AA, Wozniak TM, Shklovskaya E, O'Donnell MA, Fazekas de St Groth B, Britton WJ, Triccas JA
- Issue date: 2007 Dec 15
- Modulation of pulmonary DC function by vaccine-encoded GM-CSF enhances protective immunity against Mycobacterium tuberculosis infection.
- Authors: Nambiar JK, Ryan AA, Kong CU, Britton WJ, Triccas JA
- Issue date: 2010 Jan