Impairment of alternative macrophage activation delays cutaneous leishmaniasis in nonhealing BALB/c mice

Christoph Hölscher, Berenice Arendse, Anita Schwegmann, Elmarie Myburgh, Frank Brombacher

Research output: Contribution to journalArticlepeer-review

Abstract

Expressed on various cell types, the IL-4Ralpha is a component of both receptors for IL-4 and IL-13. Susceptibility of BALB/c mice to Leishmania major is believed to be dependent on the development of IL-4- and IL-13-producing Th2 cells, while IFN-gamma secretion by Th1 cells is related to resistance. Despite a sustained development of Th2 cells, IL-4Ralpha-deficient BALB/c mice are able to control acute cutaneous leishmaniasis, suggesting that IL-4Ralpha-bearing cells other than Th2 cells contribute to susceptibility. To analyze the contribution of the IL-4Ralpha on macrophages, recently generated macrophage/neutrophil-specific IL-4Ralpha-deficient mice on a susceptible BALB/c genetic background were infected with L. major. Strikingly, macrophage/neutrophil-specific IL-4Ralpha-deficient mice showed a significantly delayed disease progression with normal Th2 and type 2 Ab responses but improved macrophage leishmanicidal effector functions and reduced arginase activity. Together, these results suggest that alternative macrophage activation contributes to susceptibility in cutaneous leishmaniasis.

Original languageEnglish
Pages (from-to)1115-21
Number of pages7
JournalJournal of Immunology
Volume176
Issue number2
DOIs
Publication statusPublished - 15 Jan 2006

Keywords

  • Animals
  • Antibodies, Protozoan/biosynthesis
  • Interferon-gamma/biosynthesis
  • Interleukin-4/biosynthesis
  • Leishmania major/immunology
  • Leishmaniasis, Cutaneous/etiology
  • Macrophage Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cell Surface/deficiency
  • Recombinant Proteins/pharmacology
  • Th1 Cells/immunology
  • Th2 Cells/immunology

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