Advertisement

The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level

Authors

  • A. M. Ghaemmaghami,

    1. Division of Molecular & Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
    Search for more papers by this author
  • L. Gough,

    1. Division of Molecular & Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
    Search for more papers by this author
  • H. F. Sewell,

    1. Division of Molecular & Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
    Search for more papers by this author
  • F. Shakib

    1. Division of Molecular & Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
    Search for more papers by this author

Dr Farouk Shakib, Division of Molecular & Clinical Immunology, Faculty of Medicine & Health Sciences, Queen's Medical Centre, Nottingham NG7 2UH, UK. E-mail: farouk.shakib@nottingham.ac.uk

Summary

Background The proteolytic activity of the house dust mite allergen Der p 1 has recently been shown to bias Th cell subset development in favour of Th2. Apart from its direct effect on T cells, it is conceivable that the proteolytic activity of Der p 1 may induce the generation of dendritic cells (DCs) that favour a Th2 response.

Objective To study the effect of the proteolytic activity of Der p 1 on DC functions; namely cell surface phenotype, IL-12 production and ability to favour a Th2 response.

Methods We have generated immature DCs from peripheral blood monocytes, matured them with LPS in the presence of either proteolytically active or inactive Der p 1 and compared their functions using flow cytometric analysis.

Results Here we demonstrate for the first time that DCs that have been matured in the presence of proteolytically active Der p 1 produce significantly less IL-12, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. The suppression of IL-12 production was due to the cleavage of CD40 by the proteolytic activity of Der p 1, hence rendering the DCs less responsive to stimulation through the CD40L-CD40 pathway. Furthermore, we demonstrate that DCs that have been matured in the presence of proteolytically active Der p 1 induce the production of significantly less IFN-γ and more IL-4 by CD4 T cells, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1.

Conclusions Collectively, our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in directing DCs to induce Th2 subset development.

Ancillary