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

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 IL4Ra expression on macrophages/neutrophils (in LysMIL-4Ra animals) had minimal effect on the outcome of L. mexicana infection compared with control (IL-4Ra) mice. In contrast, CD4 T cell specific (LckIL-4Ra) IL-4Ra 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-4Ra 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 (iLckIL-4Ra) IL-4Ra 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. Citation: Bryson KJ, Millington OR, Mokgethi T, McGachy HA, Brombacher F, et al. (2010) 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. PLoS Negl Trop Dis 5(1): e930. doi:10.1371/journal.pntd.0000930 Editor: Genevieve Milon, Institut Pasteur, France Received July 2, 2010; Accepted December 1, 2010; Published January 4, 2011 Copyright: 2010 Bryson et al. This 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. Funding: This work was supported by grants from the Wellcome Trust; the Royal Society, UK; and the National Research Foundation, South Africa. ORM is an RCUK Academic Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]