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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

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...

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Detalles Bibliográficos
Autores principales: Bryson, Karen J., Millington, Owain R., Mokgethi, Thabang, McGachy, H. Adrienne, Brombacher, Frank, Alexander, James
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014948/
https://www.ncbi.nlm.nih.gov/pubmed/21245915
http://dx.doi.org/10.1371/journal.pntd.0000930
Descripción
Sumario: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.