Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Abrogation of IL-4 receptor-a-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing t
h
2 response
International Immunology, Volume 25, No. 8, Year 2013
Notification
URL copied to clipboard!
Description
In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4 receptor α (IL-4Rα)- dependent polyfunctional Th2 cells induce disease progression associated with alternative activation of lung macrophages. To characterize the effector role of IL-4Rα-dependent alternatively activated macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL-4Ra expression on macrophages (LysMCreIL-4Rα-/lox mice) and IL-4Rα-/lox littermates. LysMCreIL-4Rα-/lox mice were significantly more resistant to pulmonary cryptococcosis with higher survival rates and lower lung burden than non-deficient heterozygous littermates. Infected LysMCreIL-4Rα-/lox mice had reduced but detectable numbers of aaMph expressing arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression of inducible nitric oxide synthase was found in LysMCreIL-4Rα-/lox and IL-4Rα-/lox control mice, but macrophages from LysMCreIL-4Rα-/lox mice showed a higher potential to produce nitric oxide. In contrast to the differences in the macrophage phenotype, pulmonary Th2 responses were similar in infected LysMCreIL-4Rα-/lox and IL-4Rα-/lox mice with each mouse strain harboring polyfunctional Th2 cells. Consistently, type 2 pulmonary allergic inflammation associated with eosinophil recruitment and epithelial mucus production was present in lungs of both LysMCreIL- 4Rα-/lox and IL-4Ra-/lox mice. Our results demonstrate that, despite residual IL-4Rα-independent alternative macrophage activation and ongoing Th2-dependent allergic inflammation, abrogation of IL-4Ra-dependent aaMph is sufficient to confer resistance in pulmonary cryptococcosis. This is even evident on a relatively resistant heterozygous IL-4Rα+/- background indicating a key contribution of macrophage IL-4Rα expression to susceptibility in allergic bronchopulmonary mycosis. © The Japanese Society for Immunology.2013.
Authors & Co-Authors
Müller, Uwe
Germany, Leipzig
Universität Leipzig
Stenzel, Werner Peter
Germany, Berlin
Charité – Universitätsmedizin Berlin
Piehler, Daniel
Germany, Leipzig
Universität Leipzig
Grahnert, Andreas
Germany, Leipzig
Universität Leipzig
Protschka, Martina
Germany, Leipzig
Universität Leipzig
Köhler, Gabriele
Germany, Munster
Gerhard-domagk-institut Für Pathologie
Frey, O.
Germany, Jena
Universitätsklinikum Jena Und Medizinische Fakultät
Held, J.
Germany, Berlin
Charité – Universitätsmedizin Berlin
Richter, Tina
Germany, Leipzig
Universität Leipzig
Eschke, Maria
Germany, Leipzig
Universität Leipzig
Kamradt, Thomas
Germany, Jena
Universitätsklinikum Jena Und Medizinische Fakultät
Brombacher, Frank
South Africa, Cape Town
University of Cape Town
Alber, Gottfried
Germany, Leipzig
Universität Leipzig
Statistics
Citations: 38
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.1093/intimm/dxt003
ISSN:
09538178
e-ISSN:
14602377
Research Areas
Genetics And Genomics