TITLE

A Gene-Dosage Effect for Interleukin-4 Receptor α-Chain Expression Has an Impact on Th2- Mediated Allergic Inflammation during Bronchopulmonary Mycosis

AUTHOR(S)
Müller, Uwe; Stenzel, Werner; Köhler, Gabriele; Polte, Tobias; Blessing, Manfred; Mann, Amrit; Piehler, Daniel; Brombacher, Frank; Alber, Gottfried
PUB. DATE
December 2008
SOURCE
Journal of Infectious Diseases;12/1/2008, Vol. 198 Issue 11, p1714
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 receptorα-chain (IL-4Rα). In this study, we investigated the role played by IL-4Rα expression in susceptibility to pulmonary C. neoformans infection. IL- 4Rα-/- mice were extremely resistant.Tocharacterize the effect of IL-4Rα expression levelondisease outcome,we generated IL-4Rα+-/- first-generation (F1) mice. IL-4Rα+-/- mice showed intermediate levels of IL-4Rα expression, in contrast to higher levels in wild-type mice and no expression in IL-4Rα-/- mice, indicating biallelic expression of the gene for IL-4Rα (Il4ra). Concomitant with intermediate IL-4Rα 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-4Rα expression on susceptibility to bronchopulmonary mycosis. These data provide the basis for novel therapies antagonizing IL-4Rα in Th2-related pulmonary infection and possibly also in asthma.
ACCESSION #
35442728

 

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