Vacina de Bordetella pertussis reduz IgE específica, inflamação e remodelamento num modelo animal de alergia respiratória induzida por ácaro
Bordetella pertussis vaccine reduces specific IgE, inflammation, and remodeling in an animal model of respiratory allergy caused by house dust mites
Marcelo Vivolo Aun; Beatriz Mangueira Saraiva-Romanholo; Francine Maria de Almeida; Thayse Regina Brüggemann; Paulo Lee Ho; Jorge Kalil; Milton de Arruda Martins; Fernanda Magalhães Arantes-Costa; Pedro Giavina-Bianchi
Resumo
Objetivo: Adjuvantes, como lipopolissacárides bacterianos, vêm sendo estudados para melhorar a eficácia da imunoterapia alérgeno-específica. A vacina de Bordetella pertussis (Pw) mostrou ter papel protetor em modelos de asma induzida por ovalbumina. Porém, seu papel na alergia a ácaros é desconhecido. Avaliamos os efeitos da vacina difteria-tétano-coqueluche (DTPw) em um modelo murino de alergia respiratória induzida por Dermatophagoides pteronyssinus (Derp). Métodos: Num protocolo de 30 dias, camundongos BALB/c foram imunizados por via subcutânea com salina ou Derp, isoladamente ou associados às vacinas de difteria-tétano (DT) ou DTPw (dias 0, 7 e 14). Posteriormente, os animais sofreram desafio intranasal diariamente com salina ou Derp (dias 22 a 28) e foram sacrificados (dia 29). Avaliamos imunoglobulinas séricas específicas, celularidade no lavado bronco-alveolar (BAL), remodelamento das vias aéreas inferiores, densidade de leucócitos polimorfonucleares (PMN) e área de muco ácido no epitélio nasal. Resultados: Os animais sensibilizados com Derp produziram altos níveis de imunoglobulinas específicas, apresentaram aumento da densidade de PMN e da área de muco ácido nasal, elevação da celularidade no BAL e remodelamento. As vacinas levaram à redução dos níveis de IgE, sendo o grupo Derp-DTPw similar aos grupos salina. Os grupos vacinados tiveram redução da celularidade no BAL e do remodelamento, com resultados mais expressivos no grupo Derp-DTPw em relação ao Derp-DT. As vacinas DT e DTPw inibiram o infiltrado PMN nasal e DTPw modulou a produção do muco ácido. Conclusões: A vacina DTPw diminuiu a IgE específica sérica, inflamação nasal e pulmonar e o remodelamento das vias respiratórias inferiores.
Palavras-chave
Abstract
Objective: Adjuvant therapies, such as the use of bacterial lipopolysaccharides, have been evaluated as tools to improve the effectiveness of allergen-specific immunotherapy. Bordetella pertussis vaccine (Pw) has been shown to have a protective role in asthma models induced by ovalbumin. Conversely, its role in allergy to dust mites is unknown. We evaluated the effects of diphtheria-tetanus-pertussis vaccine (DTPw) in a murine model of respiratory allergy induced by Dermatophagoides pteronyssinus (Derp). Methods: Over a 30-day protocol, BALB/c mice were immunized subcutaneously with saline or Derp, alone or combined with diphtheria-tetanus vaccine (DT) or DTPw (days 0, 7, and 14). Then, they were subjected to intranasal challenge with saline or Derp daily (days 22 to 28), and sacrificed on day 29. We evaluated serum specific immunoglobulins, bronchoalveolar lavage (BAL) cellularity, lower airway remodeling, density of polymorphonuclear leukocytes (PMN), and acidic mucus area in the nasal epithelium. Results: Animals sensitized to Derp produced high levels of specific immunoglobulins, showed increased PMN density and acidic mucus in the nasal mucosa, and elevated BAL cellularity and remodeling. Vaccines led to the reduction of IgE levels, with the Derp-DTPw group showing similar results to those of the saline groups. Vaccinated groups showed reduced BAL cellularity and airway remodeling, with more expressive results in the Derp-DTPw group compared to Derp-DT. DT and DTPw vaccines inhibited PMN infiltration in nasal mucosa, and DTPw modulated the production of acidic nasal mucus. Conclusions: DTPw vaccine decreased serum specific IgE, nasal and pulmonary inflammation, and lower airway remodeling.
Keywords
Referências
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Submetido em:
10/01/2017
Aceito em:
15/02/2017
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