Mycobacterium bovis Bacillus Calmette-Guérin suppresses inflammatory Th2 responses by inducing functional alteration of TSLP-activated dendritic cells

Int Immunol. 2008 Oct;20(10):1321-9. doi: 10.1093/intimm/dxn094. Epub 2008 Aug 13.

Abstract

Allergic diseases such as atopic dermatitis and asthma develop as a consequence of dysregulated T(h)2 responses. Recently, it has been demonstrated that interaction between dendritic cells (DCs) and thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine, is essential for evoking T(h)2 responses in allergy. In this study, we investigated whether Mycobacterium bovis Bacillus Calmette-Guérin (BCG), a strong T(h)1 response-inducing adjuvant, can alter the function of DCs activated by TSLP (TSLP-DCs). We demonstrated that BCG redirects TSLP-DCs away from inducing inflammatory T(h)2 cells that produce IL-4, IL-5, IL-13 and tumor necrosis factor (TNF)-alpha and toward regulatory T(h)1 cells that produce IFN-gamma and IL-10. We also demonstrated that this functional alteration of TSLP-DCs by BCG depended on both production of IL-12 from DCs and down-regulation of OX40 ligand, a member of the TNF family, on DCs. These findings suggest that BCG might be a useful adjuvant for the treatment of allergic diseases that are triggered by TSLP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BCG Vaccine / immunology*
  • BCG Vaccine / therapeutic use
  • Cell Differentiation / immunology
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / microbiology
  • Humans
  • Hypersensitivity / immunology
  • Hypersensitivity / therapy
  • Immunosuppression Therapy
  • Immunotherapy
  • Lymphocyte Activation / immunology
  • Mycobacterium Infections / immunology*
  • Mycobacterium Infections / prevention & control
  • Mycobacterium bovis*
  • OX40 Ligand / antagonists & inhibitors
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / microbiology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Th2 Cells / microbiology
  • Thymic Stromal Lymphopoietin

Substances

  • BCG Vaccine
  • Cytokines
  • OX40 Ligand
  • Thymic Stromal Lymphopoietin