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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A gene-dosage effect for interleukin-4 receptor α-chain expression has an impact on Th2-mediated allergic inflammation during bronchopulmonary mycosis
Journal of Infectious Diseases, Volume 198, No. 11, Year 2008
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Description
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 α-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. To characterize the effect of IL-4Rα expression level on disease 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. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Müller, Uwe
South Africa, Cape Town
College of Veterinary Medicine
Stenzel, Werner Peter
Germany, Koln
Universität zu Köln
Germany, Berlin
Charité – Universitätsmedizin Berlin
Köhler, Gabriele
Germany, Munster
Gerhard-domagk-institut Für Pathologie
Polte, Tobias
South Africa, Cape Town
University of Leipzig
Blessing, Manfred
South Africa, Cape Town
College of Veterinary Medicine
Mann, Amrit
South Africa, Cape Town
College of Veterinary Medicine
Piehler, Daniel
South Africa, Cape Town
College of Veterinary Medicine
Brombacher, Frank
South Africa, Cape Town
University of Cape Town
Alber, Gottfried
South Africa, Cape Town
College of Veterinary Medicine
Germany, Leipzig
Universität Leipzig
Statistics
Citations: 9
Authors: 9
Affiliations: 7
Identifiers
Doi:
10.1086/593068
ISSN:
00221899
Research Areas
Genetics And Genomics