A gene-dosage effect for interleukin-4 receptor alpha-chain expression has an impact on Th2-mediated allergic inflammation during bronchopulmonary mycosis.
J Infect Dis
; 198(11): 1714-21, 2008 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-18954266
Interleukin (IL)-4 and IL-13 are key factors in the pathogenesis of bronchopulmonary mycosis induced in mice by infection with Cryptococcus neoformans. Both cytokines use the IL-4 receptor alpha-chain (IL-4Ralpha). In this study, we investigated the role played by IL-4Ralpha expression in susceptibility to pulmonary C. neoformans infection. IL-4Ralpha(-/-) mice were extremely resistant. To characterize the effect of IL-4Ralpha expression level on disease outcome, we generated IL-4Ralpha(+/-) first-generation (F1) mice. IL-4Ralpha(+/-) mice showed intermediate levels of IL-4Ralpha expression, in contrast to higher levels in wild-type mice and no expression in IL-4Ralpha(-/-) mice, indicating biallelic expression of the gene for IL-4Ralpha (Il4ra). Concomitant with intermediate IL-4Ralpha expression, F1 mice showed intermediate susceptibility associated with altered Th2/Th17 cytokine production, decreased immunoglobulin E levels, and reduced allergic inflammation. This indicates a gene-dosage effect of IL-4Ralpha expression on susceptibility to bronchopulmonary mycosis. These data provide the basis for novel therapies antagonizing IL-4Ralpha in Th2-related pulmonary infection and possibly also in asthma.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones del Sistema Respiratorio
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Receptores de Superficie Celular
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Células Th2
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Criptococosis
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Hipersensibilidad
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Inflamación
Límite:
Animals
Idioma:
En
Revista:
J Infect Dis
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos