balbc mice deficient in cd4+ t cell il-4rα expression control leishmania mexicana load although female but not male mice develop a healer phenotypebalbc小鼠cd4 + t细胞缺乏il-4rα表达式控制利什曼虫墨西哥负载虽然女性而不是男性老鼠开发一个治疗师表型.pdf

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 1 1 1 1 2 Karen J. Bryson , Owain R. Millington , Thabang Mokgethi , H. Adrienne McGachy , Frank Brombacher , James Alexander1* 1 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom, 2 Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa 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-4Ra-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-4Ra expression in specific cellular compartments. A deficiency of IL- 4Ra expression on macrophages/neutrophils (in LysMcreIL-4Ra2/lox animals) had minimal effect on the outcome of L. mexicana infection compared with control (IL-4Ra2/flox) mice. In contrast, CD4+ T cell specific (LckcreIL-4Ra2/lox) IL-4Ra2/ 2 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-4Ra2/ 2 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-4