Requirement of M y D 88 and F as pathways for the efficacy of allergen‐free immunotherapy

• Published in: Allergy (Copenhagen) Vol. 70; no. 3; pp. 275 - 284
• Main Authors: Fonseca, D. M., Wowk, P. F., Paula, M. O., Gembre, A. F., Baruffi, M. D., Fermino, M. L., Turato, W. M., Campos, L. W., Silva, C. L., Ramos, S. G., Horn, C., Marchal, G., Arruda, L. K., Russo, M., Bonato, V. L. D.
• Format: Journal Article
• Language: English
• Published: 01.03.2015
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.12555

Abstract Background We have shown that mycobacterial antigens and CpG oligodeoxynucleotides downmodulate airway allergic inflammation by mechanisms dependent on T‐cell activation. Here, we investigated the participation of the innate response, particularly the role of MyD88 adaptor, and Fas molecules in the effectiveness of DNA‐HSP65 or CpG/culture filtrated proteins (CFP) immunotherapy. Methods Mice sensitized and challenged with Der p 1 allergen were treated with DNA‐HSP65, CpG/CFP, or with adoptively transferred cells from immunized mice. The treatment efficacy was assessed by evaluating eosinophil recruitment, antibody, and cytokine production. Results In addition to downregulating the Th2 response, DNA‐HSP65 and CpG/CFP promoted IL‐10 and IFN‐γ production. Adoptive transfer of cells from mice immunized with DNA‐HSP65 or CpG/CFP to allergic recipients downmodulated the allergic response. Notably, transfer of cells from DNA‐HSP65‐ or CpG/CFP‐immunized MyD88 −/− mice failed to reduce allergy. Additionally, for effective reduction of allergy by cells from CpG/CFP‐immunized mice, Fas molecules were required. Although DNA‐HSP65 or CpG/CFP immunization stimulated antigen‐specific production of IFN‐γ and IL‐10, the effect of DNA‐HSP65 was associated with IL‐10 while CpG/CFP was associated with IFN‐γ. Moreover, after stimulation with mycobacterial antigens plus Der p 1 allergen, cells from mite‐allergic patients with asthma exhibited similar patterns of cytokine production as those found in the lung of treated mice. Conclusions This study provides new insights on the mechanisms of allergen‐free immunotherapy by showing that both DNA‐HSP65 and CpG/CFP downregulated house dust mite‐induced allergic airway inflammation via distinct pathways that involve not only induction of mycobacterial‐specific adaptive responses but also signaling via MyD88 and Fas molecules.