BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype

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dc.contributor.authorBryson, Karen Jen_ZA
dc.contributor.authorMillington, Owain Ren_ZA
dc.contributor.authorMokgethi, Thabangen_ZA
dc.contributor.authorMcGachy, H Adrienneen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorAlexander, Jamesen_ZA
dc.date.accessioned2016-01-11T06:53:30Z
dc.date.available2016-01-11T06:53:30Z
dc.date.issued2011en_ZA
dc.description.abstractImmunologically intact BALB/c mice infected with Leishmania mexicana develop non-healing progressively growing lesions associated with a biased Th2 response while similarly infected IL-4Rα-deficient mice fail to develop lesions and develop a robust Th1 response. In order to determine the functional target(s) for IL-4/IL-13 inducing non-healing disease, the course of L. mexicana infection was monitored in mice lacking IL-4Rα expression in specific cellular compartments. A deficiency of IL-4Rα expression on macrophages/neutrophils (in LysMcreIL-4Rα−/lox animals) had minimal effect on the outcome of L. mexicana infection compared with control (IL-4Rα−/flox) mice. In contrast, CD4+ T cell specific (LckcreIL-4Rα−/lox) IL-4Rα−/− mice infected with L. mexicana developed small lesions, which subsequently healed in female mice, but persisted in adult male mice. While a strong Th1 response was manifest in both male and female CD4+ T cell specific IL-4Rα−/− mice infected with L. mexicana, induction of IL-4 was manifest in males but not females, independently of CD4+ T cell IL-4 responsiveness. Similar results were obtained using pan-T cell specific (iLckcreIL-4Rα−/lox) IL-4Rα−/− mice. Collectively these data demonstrate that upon infection with L. mexicana, initial lesion growth in BALB/c mice is dependent on non-T cell population(s) responsive to IL-4/IL-13 while progressive infection is dependent on CD4+ T cells responsive to IL-4.en_ZA
dc.identifier.apacitationBryson, K. J., Millington, O. R., Mokgethi, T., McGachy, H. A., Brombacher, F., & Alexander, J. (2011). BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype. <i>PLOS Neglected Tropical Diseases</i>, http://hdl.handle.net/11427/16280en_ZA
dc.identifier.chicagocitationBryson, Karen J, Owain R Millington, Thabang Mokgethi, H Adrienne McGachy, Frank Brombacher, and James Alexander "BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype." <i>PLOS Neglected Tropical Diseases</i> (2011) http://hdl.handle.net/11427/16280en_ZA
dc.identifier.citationBryson, K. J., Millington, O. R., Mokgethi, T., McGachy, H. A., Brombacher, F., & Alexander, J. (2011). BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype. PLoS Negl Trop Dis, 5(1), e930. doi:10.1371/journal.pntd.0000930en_ZA
dc.identifier.ris TY - Journal Article AU - Bryson, Karen J AU - Millington, Owain R AU - Mokgethi, Thabang AU - McGachy, H Adrienne AU - Brombacher, Frank AU - Alexander, James AB - Immunologically intact BALB/c mice infected with Leishmania mexicana develop non-healing progressively growing lesions associated with a biased Th2 response while similarly infected IL-4Rα-deficient mice fail to develop lesions and develop a robust Th1 response. In order to determine the functional target(s) for IL-4/IL-13 inducing non-healing disease, the course of L. mexicana infection was monitored in mice lacking IL-4Rα expression in specific cellular compartments. A deficiency of IL-4Rα expression on macrophages/neutrophils (in LysMcreIL-4Rα−/lox animals) had minimal effect on the outcome of L. mexicana infection compared with control (IL-4Rα−/flox) mice. In contrast, CD4+ T cell specific (LckcreIL-4Rα−/lox) IL-4Rα−/− mice infected with L. mexicana developed small lesions, which subsequently healed in female mice, but persisted in adult male mice. While a strong Th1 response was manifest in both male and female CD4+ T cell specific IL-4Rα−/− mice infected with L. mexicana, induction of IL-4 was manifest in males but not females, independently of CD4+ T cell IL-4 responsiveness. Similar results were obtained using pan-T cell specific (iLckcreIL-4Rα−/lox) IL-4Rα−/− mice. Collectively these data demonstrate that upon infection with L. mexicana, initial lesion growth in BALB/c mice is dependent on non-T cell population(s) responsive to IL-4/IL-13 while progressive infection is dependent on CD4+ T cells responsive to IL-4. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pntd.0000930 DP - University of Cape Town J1 - PLOS Neglected Tropical Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype TI - BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype UR - http://hdl.handle.net/11427/16280 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16280
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pntd.0000930
dc.identifier.vancouvercitationBryson KJ, Millington OR, Mokgethi T, McGachy HA, Brombacher F, Alexander J. BALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotype. PLOS Neglected Tropical Diseases. 2011; http://hdl.handle.net/11427/16280.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular 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© 2010 Bryson et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Neglected Tropical Diseasesen_ZA
dc.source.urihttp://journals.plos.org/plosntdsen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherLeishmania majoren_ZA
dc.subject.otherAmastigotesen_ZA
dc.subject.otherNeutrophilsen_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherParasitic diseasesen_ZA
dc.subject.otherLeishmaniaen_ZA
dc.titleBALB/c mice deficient in CD4 T cell IL-4Rα expression control Leishmania mexicana Load although female but not male mice develop a healer phenotypeen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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