IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection

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dc.contributor.authorGrahnert, Andreasen_ZA
dc.contributor.authorRichter, Tinaen_ZA
dc.contributor.authorPiehler, Danielen_ZA
dc.contributor.authorEschke, Mariaen_ZA
dc.contributor.authorSchulze, Biancaen_ZA
dc.contributor.authorMüller, Uween_ZA
dc.contributor.authorProtschka, Martinaen_ZA
dc.contributor.authorKöhler, Gabrieleen_ZA
dc.contributor.authorSabat, Roberten_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorAlber, Gottfrieden_ZA
dc.date.accessioned2016-01-11T06:56:11Z
dc.date.available2016-01-11T06:56:11Z
dc.date.issued2014en_ZA
dc.description.abstractCryptococcus 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.en_ZA
dc.identifier.apacitationGrahnert, A., Richter, T., Piehler, D., Eschke, M., Schulze, B., Müller, U., ... Alber, G. (2014). IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection. <i>PLoS One</i>, http://hdl.handle.net/11427/16307en_ZA
dc.identifier.chicagocitationGrahnert, Andreas, Tina Richter, Daniel Piehler, Maria Eschke, Bianca Schulze, Uwe Müller, Martina Protschka, et al "IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16307en_ZA
dc.identifier.citationGrahnert, A., Richter, T., Piehler, D., Eschke, M., Schulze, B., Müller, U., ... & Alber, G. (2013). IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection. PloS one, 9(1), e87341. doi:10.1371/journal.pone.0087341en_ZA
dc.identifier.ris TY - Journal Article AU - Grahnert, Andreas AU - Richter, Tina AU - Piehler, Daniel AU - Eschke, Maria AU - Schulze, Bianca AU - Müller, Uwe AU - Protschka, Martina AU - Köhler, Gabriele AU - Sabat, Robert AU - Brombacher, Frank AU - Alber, Gottfried AB - 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. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0087341 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection TI - IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection UR - http://hdl.handle.net/11427/16307 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16307
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0087341
dc.identifier.vancouvercitationGrahnert A, Richter T, Piehler D, Eschke M, Schulze B, Müller U, et al. IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection. PLoS One. 2014; http://hdl.handle.net/11427/16307.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Grahnert et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherCryptococcus neoformansen_ZA
dc.subject.otherDendritic cellsen_ZA
dc.subject.otherWhite blood cellsen_ZA
dc.subject.otherNitric oxideen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherAlveolar macrophagesen_ZA
dc.subject.otherCloningen_ZA
dc.subject.otherMacrophagesen_ZA
dc.titleIL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infectionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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