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Endogenous IL-13 plays a crucial role in liver granuloma maturation during Leishmania donovani infection, independent of IL-4Rα-responsive macrophages and neutrophils.

Abstract
Previous studies comparing interleukin 4 receptor α (IL-4Rα)(-/-) and interleukin 4 (IL-4)(-/-) BALB/c mice have indicated that interleukin 13 (IL-13), whose receptor shares the IL-4Rα subunit with IL-4, plays a protective role during visceral leishmaniasis. We demonstrate that IL-13(-/-) BALB/c mice were less able to control hepatic growth of Leishmania donovani compared with wild-type mice. This correlated with significantly retarded granuloma maturation in IL-13(-/-) mice, defective interferon γ (IFN-γ) production, and elevated IL-4 and interleukin 10 (IL-10) levels. L. donovani-infected IL-13(-/-) mice also responded poorly to sodium stibogluconate-mediated chemotherapy compared with wild-type BALB/c mice. Because murine lymphocytes do not have IL-13 receptors, we examined the ability of macrophage/neutrophil-specific IL-4Rα(-/-) mice to control primary infection with L. donovani and to respond to chemotherapy. Macrophage/neutrophil-specific IL-4Rα(-/-) mice were as resistant to leishmaniasis as wild-type mice, and chemotherapy retained its efficacy. Consequently, in L. donovani infected BALB/c mice, IL-13 promotes hepatic granuloma formation and controls parasite burdens independently of direct effects on macrophages/neutrophils.
AuthorsEmma McFarlane, Katharine C Carter, Andrew N McKenzie, Paul M Kaye, Frank Brombacher, James Alexander
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 204 Issue 1 Pg. 36-43 (Jul 01 2011) ISSN: 1537-6613 [Electronic] United States
PMID21628656 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Il4ra protein, mouse
  • Interleukin-13
  • Receptors, Cell Surface
Topics
  • Animals
  • Female
  • Granuloma (immunology, parasitology, pathology)
  • Interleukin-13 (deficiency, immunology)
  • Leishmania donovani (immunology, pathogenicity)
  • Leishmaniasis, Visceral (immunology, parasitology, pathology)
  • Macrophages (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neutrophils (immunology)
  • Receptors, Cell Surface (immunology)

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