RESUMO
The protective effects of mycobacterial infections on lung allergy are well documented. However, the inverse relationship between tuberculosis and type 2 immunity is still elusive. Although type 1 immunity is essential to protection against Mycobacterium tuberculosis it might be also detrimental to the host due to the induction of extensive tissue damage. Here, we determined whether lung type 2 immunity induced by allergen sensitization and challenge could affect the outcome of M. tuberculosis infection. We used two different protocols in which sensitization and allergen challenge were performed before or after M. tuberculosis infection. We found an increased resistance to M. tuberculosis only when allergen exposure was given after, but not before infection. Infected mice exposed to allergen exhibited lower bacterial load and cellular infiltrates in the lungs. Enhanced resistance to infection after allergen challenge was associated with increased gene expression of alternatively activated macrophages (M2 macrophages) and IL-33 levels. Accordingly, either adoptive transfer of M2 macrophages or systemic IL-33 treatment was effective in attenuating M. tuberculosis infection. Notably, the enhanced resistance induced by allergen exposure was dependent on IL-33 receptor ST2. Our work indicates that IL-33 might be an alternative therapeutic treatment for severe tuberculosis.
Assuntos
Interleucina-33/imunologia , Pulmão/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose/imunologia , Alérgenos/imunologia , Alérgenos/toxicidade , Animais , Carga Bacteriana/imunologia , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Interleucina-33/genética , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Tuberculose/genética , Tuberculose/microbiologia , Tuberculose/patologia , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
The population control of dogs and cats is a public healthconcern. This report describes the activities of the AcademicExtension of the College of Agricultural and VeterinarySciences of UNESP in Jaboticabal/SP - Brazil aimed at surgicalsterilization of stray dogs and cats, with social actionsrelated to teaching and research. In 2007, the first yearof the project, 129 pets were sterilized, whereas in 2014,between January and October, 1538 animals were sterilized,which shows the increase in program acceptance by thelocal community. All the activities carried out contributedtowards the academic and professional training of studentsof the extension project, as well as residents participating inthe program. It can be concluded that the development ofsurgical sterilization programs of dogs and cats by educationalinstitutions, combining research, teaching, and extensionpractices, is a viable option for veterinary medicine teachingpractices.(AU)
O controle da população de cães e gatos é uma preocupaçãopara a saúde pública. Este relato descreve as atividades realizadasno Projeto de Extensão da Faculdade de Ciências Agrárias eVeterinárias da Universidade Estadual Paulista "Júlio de MesquitaFilho" (UNESP) de Jaboticabal, localizada no Estado de São Paulo,Brasil, que visou à esterilização cirúrgica de cães e gatos, comações sociais aliadas ao ensino e pesquisa. Em 2007, ano de implantaçãodo projeto, foram esterilizados 129 animais; já no anode 2014, entre os meses de janeiro e outubro, foram esterilizados1.538 animais, o que demonstra a evolução e aceitação do programapela sociedade local. Toda a atividade realizada colaboroupara a formação acadêmica e profissional dos alunos do projetode extensão, bem como residentes participantes do programa.Pode-se concluir que o desenvolvimento de programas para aesterilização de cães e gatos, em conjunto com instituições educacionais,aliando pesquisa às práticas de ensino e extensão, é uma opção viável para as práticas de ensino em Medicina Veterinária.(AU)
Assuntos
Animais , Gatos , Cães , Substâncias para o Controle da Reprodução/análise , Substâncias para o Controle da Reprodução/síntese química , Substâncias para o Controle da Reprodução/farmacocinética , Substâncias para o Controle da Reprodução/provisão & distribuição , Cães/metabolismo , Gatos/metabolismoRESUMO
The population control of dogs and cats is a public healthconcern. This report describes the activities of the AcademicExtension of the College of Agricultural and VeterinarySciences of UNESP in Jaboticabal/SP - Brazil aimed at surgicalsterilization of stray dogs and cats, with social actionsrelated to teaching and research. In 2007, the first yearof the project, 129 pets were sterilized, whereas in 2014,between January and October, 1538 animals were sterilized,which shows the increase in program acceptance by thelocal community. All the activities carried out contributedtowards the academic and professional training of studentsof the extension project, as well as residents participating inthe program. It can be concluded that the development ofsurgical sterilization programs of dogs and cats by educationalinstitutions, combining research, teaching, and extensionpractices, is a viable option for veterinary medicine teachingpractices.
O controle da população de cães e gatos é uma preocupaçãopara a saúde pública. Este relato descreve as atividades realizadasno Projeto de Extensão da Faculdade de Ciências Agrárias eVeterinárias da Universidade Estadual Paulista "Júlio de MesquitaFilho" (UNESP) de Jaboticabal, localizada no Estado de São Paulo,Brasil, que visou à esterilização cirúrgica de cães e gatos, comações sociais aliadas ao ensino e pesquisa. Em 2007, ano de implantaçãodo projeto, foram esterilizados 129 animais; já no anode 2014, entre os meses de janeiro e outubro, foram esterilizados1.538 animais, o que demonstra a evolução e aceitação do programapela sociedade local. Toda a atividade realizada colaboroupara a formação acadêmica e profissional dos alunos do projetode extensão, bem como residentes participantes do programa.Pode-se concluir que o desenvolvimento de programas para aesterilização de cães e gatos, em conjunto com instituições educacionais,aliando pesquisa às práticas de ensino e extensão, é uma opção viável para as práticas de ensino em Medicina Veterinária.
Assuntos
Animais , Gatos , Cães , Cães/metabolismo , Gatos/metabolismo , Substâncias para o Controle da Reprodução/análise , Substâncias para o Controle da Reprodução/farmacocinética , Substâncias para o Controle da Reprodução/provisão & distribuição , Substâncias para o Controle da Reprodução/síntese químicaRESUMO
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
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.