Requirement of MyD88 and Fas pathways for the efficacy of allergen-free immunotherapy

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Fonseca, D. M. ^[1] ; Wowk, P. F. ^{[1, 2]} ; Paula, M. O. ^[1] ; Gembre, A. F. ^[1] ; Baruffi, M. D. ^[3] ; Fermino, M. L. ^[3] ; Turato, W. M. ^[1] ; Campos, L. W. ^[1] ; Silva, C. L. ^[1] ; Ramos, S. G. ^[4] ; Horn, C. ^[5] ; Marchal, G. ^[6] ; Arruda, L. K. ^[7] ; Russo, M. ^[8] ; Bonato, V. L. D. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biochem & Immunol, Ribeirao Preto Med Sch, BR-14049 Ribeirao Preto - Brazil

^[2] Fundacao Oswaldo Cruz, Carlos Chagas Inst, Curitiba, Parana - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, BR-14049 Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, BR-14049 Ribeirao Preto - Brazil

^[5] Fundacao Oswaldo Cruz, Evandro Chagas Clin Res Inst, Lab Immunol & Immunogenet, Rio De Janeiro - Brazil

^[6] Inst Pasteur, Paris - France

^[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med, BR-14049 Ribeirao Preto - Brazil

^[8] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-14049900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ALLERGY; v. 70, n. 3, p. 275-284, MAR 2015.
• Citações Web of Science: 8

Resumo

BackgroundWe 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. MethodsMice 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. ResultsIn addition to downregulating the Th2 response, DNA-HSP65 and CpG/CFP promoted IL-10 and IFN- 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- and IL-10, the effect of DNA-HSP65 was associated with IL-10 while CpG/CFP was associated with IFN-. 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. ConclusionsThis 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. (AU)

• Processo FAPESP: 05/59198-8 - Avaliacao do efeito imunomodulador da vacina dna-hsp65 na alergia experimental.
• Beneficiário: Denise Morais da Fonseca
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 05/01995-0 - Avaliação do papel das células T regulatórias (CD4 + CD25+) em camundongos infectados com Mycobacterium tuberculosis
• Beneficiário: Vânia Luiza Deperon Bonato
• Modalidade de apoio: Auxílio à Pesquisa - Regular