Der p 2 recombinant bacille Calmette-Guérin targets dendritic cells to inhibit allergic airway inflammation in a mouse model of asthma

Respiration. 2013;85(1):49-58. doi: 10.1159/000340007. Epub 2012 Sep 26.

Abstract

Background: Previous studies showed that a recombinant bacille Calmette-Guérin (rBCG) which expressed the Der p 2 of house dust mites (Der p 2 rBCG) could suppress asthmatic airway inflammation. There are two possible mechanisms: (1) Der p 2 rBCG elicits immune deviation from Th2 to Th1, and (2) Der p 2 rBCG induces antigen-specific regulatory T cells. However, the role of dendritic cell (DC) Der p 2 rBCG in this protective effect and in reprogramming T-cell commitment still needs to be studied.

Objectives: The aim of this study was to determine whether DCs play a central role in the Der p 2 rBCG-mediated inhibition of allergic airway inflammation.

Methods: DCs were collected from Der p 2 rBCG-immunized mice (Der p 2 rBCG-DCs) and adoptively transferred to Der p 2-sensitized mice. The effects of DCs on airway inflammation and immune regulation were analyzed.

Results: Adoptive transfer of DCs from Der p 2 rBCG-immunized mice suppressed asthmatic responses, including airway inflammation, mucin secretion and airway responsiveness. Der p 2 rBCG-DCs could effectively inhibit excessive Th2 immune responses and induced a subtype of CD4+CD25+Foxp3+ anti-specific regulatory T cells in this asthma model. Furthermore, Der p 2 rBCG immunization recruited more plasmacytoid DCs in abdominal draining lymph nodes.

Conclusions: These findings suggest that DCs played a key role in Der p 2 rBCG-induced immunoregulation. Compared with BCG, Der p 2 rBCG displayed a more potent inhibitory effect on asthma responses, which may be related to the increase in plasmacytoid DC recruitment. These results improve our understanding of the cellular basis of Der p 2 BCG-mediated inhibition of asthma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / immunology
  • Antigens, Dermatophagoides / therapeutic use*
  • Arthropod Proteins / immunology
  • Arthropod Proteins / therapeutic use*
  • Asthma / immunology
  • Asthma / pathology
  • Asthma / therapy*
  • BCG Vaccine / immunology
  • BCG Vaccine / therapeutic use*
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Female
  • Immunotherapy, Adoptive / methods*
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • BCG Vaccine
  • Dermatophagoides pteronyssinus antigen p 2
  • Recombinant Fusion Proteins