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BALB/c Mice Deficient in CD4+T Cell IL-4Ra Expression Control Leishmania mexicana Load although Female but Not Male Mice Develop a Healer Phenotype

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  • Karen Bryson
  • Owain Millington
  • T Mokgethi
  • Helen McGachy
  • F Brombacher
  • James Alexander

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http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000930
Original languageEnglish
Article numbere930
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number1
DOIs
StatePublished - 4 Jan 2011

Abstract

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 LysM(cre)IL-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 (Lck(cre)IL-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 (iLck(cre)IL-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.

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