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- Title
IL-4 Receptor-Alpha-Dependent Control of <i>Cryptococcus neoformans</i> in the Early Phase of Pulmonary Infection.
- Authors
Grahnert, Andreas; Richter, Tina; Piehler, Daniel; Eschke, Maria; Schulze, Bianca; Müller, Uwe; Protschka, Martina; Köhler, Gabriele; Sabat, Robert; Brombacher, Frank; Alber, Gottfried
- Abstract
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.
- Subjects
INTERLEUKIN-4 receptors; CRYPTOCOCCUS neoformans; LUNG infections; PATHOGENIC fungi; MENINGOENCEPHALITIS; LABORATORY mice; IMMUNE response
- Publication
PLoS ONE, 2014, Vol 9, Issue 1, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0087341