Recombinant DNA immunotherapy ameliorate established airway allergy in a IL-10 dependent pathway

• Published in: Clinical and experimental allergy 2012-01, Vol.42 (1), p.131-143
• Main Authors: Fonseca, D. M., Wowk, P. F., Paula, M. O., Campos, L. W., Gembre, A. F., Turato, W. M., Ramos, S. G., Dias-Baruffi, M., Barboza, R., Gomes, E., Silva, C. L., Russo, M., Bonato, V. L. D.
• Format: Article
• Language: English
• Subjects: airway allergic inflammation; Allergens; Allergic diseases; Animal models; Animals; Antiinflammatory agents; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Biological and medical sciences; Chaperonin 60 - genetics; Chaperonin 60 - immunology; Disease Models, Animal; DNA; DNA, Recombinant - administration & dosage; DNA, Recombinant - immunology; Eosinophilia; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; heat shock protein; Heat shock proteins; Helper cells; Hsp65 protein; Humans; Hypersensitivity; Immunoregulation; Immunotherapy; Immunotherapy - methods; Infection; Inflammation; Interleukin 10; Interleukin-10 - immunology; Interleukin-10 - metabolism; Leukocyte migration; Lung diseases; Lymphocytes T; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Mucus; Mycobacterium; Mycobacterium leprae - immunology; Ovalbumin; Plasmids; recombinant DNA; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - therapy; Respiratory tract; Treatment Outcome
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2011.03845.x

Summary Background Previous studies have established that mycobacterial infections ameliorate allergic inflammation. However, a non‐infectious approach that controls allergic responses might represent a safer and more promising strategy. The 60–65 kDa heat shock protein (Hsp) family is endowed with anti‐inflammatory properties, but it is still unclear whether and how single mycobacterial Hsp control allergic disorders. Objective Therefore, in this study we determined whether the administration of Mycobacterial leprae Hsp65 expressed by recombinant a DNA plasmid could attenuate a previously established allergic response. Methods We used an experimental model of airway allergic inflammation to test the effects of immunotherapy with DNA encoding Hsp65. Allergic mice, previously sensitized and challenged with ovalbumin, were treated with tree intramuscular doses of recombinant DNA encoding Hsp65. After treatment, mice received a second allergen challenge and the allergic response was measured. Results We found that immunotherapy attenuated eosinophilia, pulmonary inflammation, Th2 cytokine and mucus production. Moreover, we showed that the inhibition of allergic response is dependent on IL‐10 production. Both Hsp65 and allergen‐specific IL‐10‐producing cells contributed to this effect. Cells transferred from DNA‐immunized mice to allergic mice migrated to allergic sites and down‐modulated the Th2 response. Conclusions and Clinical Relevance Our findings clearly show that immunotherapy with DNA encoding Hsp65 can attenuate an established Th2 allergic inflammation through an IL‐10‐dependent mechanism; moreover, the migration of allergen‐ and Hsp65‐specific cells to the allergic sites exerts a fundamental role. This work represents a novel contribution to the understanding of immune regulation by Hsp65 in allergic diseases.