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

McFarlane, Emma and Carter, Katharine C and McKenzie, Andrew N and Kaye, Paul M and Brombacher, Frank and Alexander, James (2011) Endogenous IL-13 plays a crucial role in liver granuloma maturation during Leishmania donovani infection, independent of IL-4R alpha-responsive macrophages and neutrophils. Journal of Infectious Diseases, 204 (1). pp. 36-43.

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Abstract

Previous studies comparing interleukin 4 receptor alpha (IL-4R alpha)(-/-) and interleukin 4 (IL-4)(-/-) BALB/c mice have indicated that interleukin 13 (IL-13), whose receptor shares the IL-4R alpha 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 gamma (IFN-gamma) 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-4R alpha(-/-) mice to control primary infection with L. donovani and to respond to chemotherapy. Macrophage/neutrophil-specific IL-4R alpha(-/-) 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.

Item type: Article
ID code: 32432
Keywords: macrophages, Leishmania donovani, animals, Interleukin-13, neutrophils, mice, Leishmaniasis, visceral, mice, inbred BALB C, Granuloma, receptors, cell surface, female, mice, knockout, Pharmacy and materia medica, Pharmacology, Toxicology and Pharmaceutics(all)
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 05 Aug 2011 11:29
    Last modified: 12 Sep 2014 05:04
    URI: http://strathprints.strath.ac.uk/id/eprint/32432

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