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

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

Research output: Contribution to journalArticle

34 Citations (Scopus)

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
Externally publishedYes

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Leishmania major
Interleukin-4
Infection
Interleukin-13
129 Strain Mouse
Parasite Load
Cytokines
Inbred Strains Mice
Parasites

ASJC Scopus subject areas

  • Immunology

Cite this

BCL-6-deficient mice reveal an IL-4-independent, STAT6-dependent pathway that controls susceptibility to infection by Leishmania major. / Dent, Alexander; Doherty, T. Mark; Paul, William E.; Sher, Alan; Staudt, Louis M.

In: Journal of Immunology, Vol. 163, No. 4, 15.08.1999, p. 2098-2103.

Research output: Contribution to journalArticle

Dent, Alexander ; Doherty, T. Mark ; Paul, William E. ; Sher, Alan ; Staudt, Louis M. / BCL-6-deficient mice reveal an IL-4-independent, STAT6-dependent pathway that controls susceptibility to infection by Leishmania major. In: Journal of Immunology. 1999 ; Vol. 163, No. 4. pp. 2098-2103.
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