RESUMO
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.
Assuntos
Hipersensibilidade/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais , Receptor fas/metabolismo , Alérgenos/imunologia , Animais , Antígenos de Bactérias/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/genética , Asma/imunologia , Asma/metabolismo , Asma/terapia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Cisteína Endopeptidases/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoterapia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Knockout , Mycobacterium/imunologia , Fator 88 de Diferenciação Mieloide/genética , Oligodesoxirribonucleotídeos/administração & dosagem , Pyroglyphidae/imunologia , Baço/citologia , Baço/imunologia , Baço/metabolismo , Receptor fas/genéticaRESUMO
The aim of this study was to investigate whether Toxocara canis infection in guinea pigs provokes changes in ileum responsiveness to histamine. Ileum segments from control and T. canis-infected groups were placed at isometric conditions and submitted to various doses of histamine. No changes were observed between controls and T. canis-infected groups at days 3, 6 and 12 after infection. However, at days 18 and 24 after infection, there was a significant increase in ileum responsiveness to histamine in T. canis-infected group. Pre-incubation of ileum segments with 1mgml(-1) disodium cromoglycate (DSCG) prevented the increased responsiveness to histamine in T. canis-infected guinea pigs and did not affect ileum contractility in non-infected animals. These results indicate that T. canis-infected guinea pigs develop increased intestinal responsiveness to histamine and that DSCG prevents alterations in smooth-muscle contractility.