BALB/c mice deficient in CD4(+) T cell IL-4R alpha expression control Leishmania mexicana load although female but not male mice develop a healer phenotype

Karen Bryson, Owain Millington, Thabang Mokgethi, Adrienne McGachy, Frank Brombacher, James Alexander

Research output: Contribution to journalArticle

11 Citations (Scopus)
37 Downloads (Pure)

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-4R alpha-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-4R alpha expression in specific cellular compartments. A deficiency of IL-4R alpha expression on macrophages / neutrophils (in LysM(cre)IL-4R alpha(-lox) animals) had minimal effect on the outcome of L. mexicana infection compared with control (IL-4R alpha(-/flox)) mice. In contrast, CD4(+) T cell specific (Lys(cre)IL-4R alpha(-lox)) IL-4R alpha(-/-) 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-4R alpha(-/-) 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-4R alpha(-/lox)) IL-4R alpha(-/-) 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.

Original languageEnglish
Article numbere930
Pages (from-to)1-10
Number of pages10
JournalPLOS Neglected Tropical Diseases
Volume5
Issue number1
DOIs
Publication statusPublished - 4 Jan 2011

Keywords

  • animals
  • interleukin-13
  • sex factors
  • mice
  • leishmaniasis, cutaneous
  • mice, inbred BALB C
  • receptors, cell surface
  • CD4-positive T-lymphocytes
  • mice, knockout
  • interleukin-4
  • leishmania mexicana
  • female
  • male

Cite this