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Attenuation of experimental asthma by mycobacterial protein combined with CpG requires a TLR 9‐dependent IFN ‐γ‐ CCR 2 signalling circuit
Author(s) -
Prado R. Q.,
Bertolini T. B.,
Piñeros A. R.,
Gembre A. F.,
Ramos S. G.,
Silva C. L.,
Borges M. C.,
Bonato V. L. D.
Publication year - 2015
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12564
Subject(s) - immunology , immune system , ovalbumin , medicine , immunotherapy , allergy , asthma , cpg site , innate immune system , biology , dna methylation , biochemistry , gene expression , gene
Summary Background Allergic asthma is a chronic pulmonary disease characterized by a Th2 inflammatory response. The modulation of a Th2 immune response based on immune deviation to a Th1 pattern or induction and migration of regulatory T cells to the lungs constitutes one of the major therapeutic approaches that is being investigated for the treatment of allergic asthma. The potentials of Mycobacterium leprae 65‐ kD heat‐shock protein or Toll‐like receptor 9 ligand (CpG oligodeoxynucleotides) as immune modulators for the treatment of airway allergic disease have been studied individually. Objective Mycobacterial protein combined with CpG was used as immunotherapy for airway allergy. Methods Using an ovalbumin‐induced asthma model, mice were sensitized and challenged, and then treated with mycobacterial heat‐shock protein (Hsp65) combined with CpG. Results The treatment of mice with established allergy led to the attenuation of eosinophilia, Th2 cytokines and airway hyperresponsiveness. Hsp65 plus CpG treatment also induced an increase in OVA ‐specific IFN ‐γ levels and in the frequency of lung inflammatory monocytes. Moreover, we show that the reduction of eosinophilia and the recruitment of inflammatory monocytes to the lungs required early triggering of TLR 9, IFN ‐γ and CCR 2 by immunotherapy components. Conclusion In addition to immune deviation to a Th1 response in the modulation of Th2 allergic inflammation, our findings also attribute an important role to the innate response mediated by TLR 9, associated with the recruitment of CCR 2‐dependent monocytes. Clinical Relevance Our findings show that the Hsp65/CpG treatment is a promising strategy for consideration in translational studies.