BCL-6-deficient mice reveal an IL-4-independent, STAT6-dependent pathway that controls susceptibility to infection by Leishmania major

Alexander L. Dent, T. Mark Doherty, William E. Paul, Alan Sher, Louis M. Staudt

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The BCL-6 gene negatively regulates Th2 responses as shown by the finding that BCL-6-deficient (BCL-6(-/-)) mice develop a lethal Th2-type inflammatory disease. The response of inbred mouse strains to infection with Leishmania major is under genetic control; BALB/c mice are susceptible and develop a progressive parasite burden, whereas most other common laboratory strains of mice are resistant to infection. We found that BCL-6(-/-) mice on a resistant genetic background (C57BL/6 x 129 intercrossed mice) were highly susceptible to L. major infection; they resembled BALB/c mice in terms of lesion size, parasite load, and the production of Th2 cytokines. BCL-6(-/- )IL-4(-/-) double-mutant mice were also susceptible to L. major infection and produced 10-fold higher levels of the Th2 cytokine IL-13 than IL-4(-/-) littermate controls. By contrast, BCL-6(-/-)STAT6(-/-) double-mutant mice were resistant to L. major infection despite also producing elevated levels of IL-13. These results show that STAT6 is required for susceptibility to L. major infection and suggest that IL-13 signaling through STAT6 may contribute to a nonhealing, exacerbated L. major infection.

Original languageEnglish (US)
Pages (from-to)2098-2103
Number of pages6
JournalJournal of Immunology
Volume163
Issue number4
StatePublished - Aug 15 1999

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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