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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
IL-4 Receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection
PLoS ONE, Volume 9, No. 1, Article e87341, Year 2014
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Description
Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised people. Previously we showed that mice succumb to intranasal infection by induction of pulmonary interleukin (IL)-4Rα-dependent type 2 immune responses, whereas IL-12-dependent type 1 responses confer resistance. In the experiments presented here, IL-4Rα-/- mice unexpectedly show decreased fungal control early upon infection with C. neoformans, whereas wild-type mice are able to control fungal growth accompanied by enhanced macrophage and dendritic cell recruitment to the site of infection. Lower pulmonary recruitment of macrophages and dendritic cells in IL-4Rα-/- mice is associated with reduced pulmonary expression of CCL2 and CCL20 chemokines. Moreover, IFN-γ and nitric oxide production are diminished in IL-4Rα-/- mice compared to wild-type mice. To directly study the potential mechanism(s) responsible for reduced production of IFN-γ, conventional dendritic cells were stimulated with C. neoformans in the presence of IL-4 which results in increased IL-12 production and reduced IL-10 production. Together, a beneficial role of early IL-4Rα signaling is demonstrated in pulmonary cryptococcosis, which contrasts with the well-known IL-4Rα-mediated detrimental effects in the late phase. © 2014 Grahnert et al.
Authors & Co-Authors
Grahnert, Andreas
Germany, Leipzig
Universität Leipzig
Richter, Tina
Germany, Leipzig
Universität Leipzig
Piehler, Daniel
Germany, Leipzig
Universität Leipzig
Eschke, Maria
Germany, Leipzig
Universität Leipzig
Schulze, Bianca
Germany, Leipzig
Universität Leipzig
Müller, Uwe
Germany, Leipzig
Universität Leipzig
Protschka, Martina
Germany, Leipzig
Universität Leipzig
Köhler, Gabriele
Germany, Munster
Gerhard-domagk-institut Für Pathologie
Sabat, Robert
Germany, Berlin
Charité – Universitätsmedizin Berlin
Brombacher, Frank
South Africa, Cape Town
University of Cape Town
Alber, Gottfried
Germany, Leipzig
Universität Leipzig
Statistics
Citations: 24
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1371/journal.pone.0087341
e-ISSN:
19326203