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J Leukoc Biol ; 106(3): 653-664, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31329326

RESUMO

Blomia tropicalis mite is highly prevalent in tropical and subtropical regions and it is associated with allergic diseases such as rhinitis and asthma. By using an OVA-model of allergic lung disease, we have previously shown that sensitization in the presence of toll like receptors (TLRs) agonists attenuates subsequent OVA-induced allergic responses. Here, we evaluated the effect of CpG-ODN, a specific synthetic TLR-9 agonist, on the development of experimental asthma induced by Blomia tropicalis extract, a relevant source of aeroallergens. Among different protocols of Blomia tropicalis extract sensitization, the subcutaneous sensitization in the presence of alum adjuvant induced the highest Th2 responses, including high IgE levels. Adsorption of CpG to Blomia tropicalis extract/Alum attenuated the airway hyperreactivity, the infiltration of inflammatory cells including eosinophils, and the IL-5 content in BAL. In addition, lung peribronchial inflammatory infiltrate, mucus production and IL-5-producing CD3+ CD4+ T cells were significantly reduced in the Blomia tropicalis extract/Alum+CpG group. Importantly, CpG inhibited total IgE production as well as active systemic or cutaneous anaphylaxis reactions. Inhibition of pulmonary Th2 responses was associated with increased IL-10 production but not with IFN-γ production. Notably, in IL-10-deficient mice, sensitization with OVA/Alum+CpG resulted in intense lung neutrophilia and IFN-γ production, indicating that IL-10 is necessary to inhibit subsequent Th1 immunity. Our work highlights the mechanisms of allergy attenuation by CpG and it indicates the potential use of Alum-based formulation with CpG to treat allergic processes.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Compostos de Alúmen/química , Asma/prevenção & controle , Asma/parasitologia , Pyroglyphidae/fisiologia , Receptor Toll-Like 9/agonistas , Adjuvantes Imunológicos/farmacologia , Adsorção , Anafilaxia/complicações , Anafilaxia/imunologia , Anafilaxia/parasitologia , Animais , Asma/complicações , Citocinas/biossíntese , Modelos Animais de Doenças , Eosinófilos/patologia , Feminino , Hipersensibilidade/complicações , Hipersensibilidade/imunologia , Hipersensibilidade/parasitologia , Imunidade/efeitos dos fármacos , Imunização , Interleucina-10/metabolismo , Interleucina-4/biossíntese , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/patologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Camundongos Endogâmicos C57BL , Neutrófilos/patologia , Oligodesoxirribonucleotídeos/farmacologia , Pyroglyphidae/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Receptor Toll-Like 9/metabolismo
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