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Doctoral Thesis
DOI
10.11606/T.42.2010.tde-13012011-164628
Document
Author
Full name
Renato Barboza
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Russo, Momtchilo (President)
Bozza, Marcelo Torres
Câmara, Niels Olsen Saraiva
Martins, Vania Luiza Deperon Bonato
Starobinas, Nancy
Title in Portuguese
Influência dos receptores do tipo Toll 2 e 4 no desenvolvimento da alergia pulmonar experimental induzida por Blomia tropicalis em presença de lipopolissacarídio.
Keywords in Portuguese
Ácaro
Alergia e Imunologia
Asma
Receptores imunológicos
Abstract in Portuguese
O objetivo deste trabalho foi estudar o efeito da endotoxina durante a sensibilização com extrato de Blomia tropicalis (Bt) Para induzir a alergia pulmonar experimental, camundongos foram sensibilizados s.c. com Bt adsorvido ao alum em presença ou não de LPS e desafiados i.n. com Bt. Os animais sensibilizados e desafiados com de Bt apresentaram intensa inflamação pulmonar eosinofílica, AHR, grande produção de muco, aumento na produção de citocinas do tipo 2 no lavado broncoalveolar (BAL) e aumento de IgE. Quando o LPS foi adicionado, observou-se inibição no influxo de eosinófilos e aumento no influxo de neutrófilos no BAL. O LPS também inibiu IL-4 e IL5 e aumentou IFNg e IL-17. Surpeendentemente, o LPS não afetou a AHR, nem a produção de IgE. Utilizando animais nocautes, verificou-se que a inibição eosinofílica induzida pelo LPS é dependente de IFNg e MyD88 enquanto que o aumento de neutrófilos é independente de IFNg e dependente da sinalização dos TLR2, TLR4 e CD14. Além disso, na ausência de TLR2, TLR4 ou CD14, o LPS suprimiu a alergia pulmonar experimental. Em conclusão, os resultados indicam que camundongos sensibilizados com Bt e LPS co-adsorvidos ao alum desenvolvem um fenótipo de asma não clássico, dependente da sinalização pelos TLR.
Title in English
Influence of Toll-like receptors 2 and 4 on the development of experimental allergic airway disease induced by Blomia tropicalis in the presence of lipopolissacharide.
Keywords in English
Allergy and immunology
Asthma
Immunogical receptores
Mite
Abstract in English
The aim of this work was to study the effects of endotoxin during sensitization with Blomia tropicalis extract (Bt). To induce experimental allergic airways, mice were sensitized s.c. with Bt with or without LPS co-adsorbed onto alum, and challenged i.n. with Bt. Wild type mice sensitized and challenged with HDM showed eosinophilic lung inflammation, Arway hyperactivity (AHR), mucus hyperproduction, increased levels of type 2 cytokines in the bronchoalveolar lavage (BAL) fluid, and augmented total IgE. When LPS was added at the sensitization, we observed an inhibition of eosinophil influx and an increase in neutrophil counts in the BAL. Moreover, LPS inhibited IL-4 and IL-5 production and increased IFN-g and IL-17 production. Surprisingly, LPS did not affect AHR or IgE production. Using knockout mice, we found that the eosinophilic inhibition induced by LPS was dependent on IFNg and MyD88, while the neutrophilic increase was independent of IFNg and dependent on TLR2, TLR4 and CD14 signaling. Moreover, in the absence of TLR2, TLR4 or CD14, LPS suppressed AAD. In conclusion, our results indicate that mice sensitized with Bt and LPS co-adsorbed to alum develop a non-classical asthma-like phenotype that is dependent on TLR signaling.
 
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Publishing Date
2011-08-08
 
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