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

Emma McFarlane, Katharine C Carter, Andrew N McKenzie, Paul M Kaye, Frank Brombacher, James Alexander

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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.

LanguageEnglish
Pages36-43
Number of pages8
JournalJournal of Infectious Diseases
Volume204
Issue number1
DOIs
Publication statusPublished - 1 Jul 2011

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Interleukin-4 Receptor alpha Subunit
Leishmania donovani
Interleukin-13
Granuloma
Neutrophils
Macrophages
Liver
Infection
Interleukin-13 Receptors
Interleukin-4
Drug Therapy
Antimony Sodium Gluconate
Communicable Disease Control
Leishmaniasis
Visceral Leishmaniasis
Infection Control
Interleukin-10
Interferon-gamma

Keywords

  • macrophages
  • Leishmania donovani
  • animals
  • Interleukin-13
  • neutrophils
  • mice
  • Leishmaniasis, visceral
  • mice, inbred BALB C
  • Granuloma
  • receptors, cell surface
  • female
  • mice, knockout

Cite this

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title = "Endogenous IL-13 plays a crucial role in liver granuloma maturation during Leishmania donovani infection, independent of IL-4R alpha-responsive macrophages and neutrophils",
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.",
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AU - McFarlane, Emma

AU - Carter, Katharine C

AU - McKenzie, Andrew N

AU - Kaye, Paul M

AU - Brombacher, Frank

AU - Alexander, James

PY - 2011/7/1

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N2 - 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.

AB - 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.

KW - macrophages

KW - Leishmania donovani

KW - animals

KW - Interleukin-13

KW - neutrophils

KW - mice

KW - Leishmaniasis, visceral

KW - mice, inbred BALB C

KW - Granuloma

KW - receptors, cell surface

KW - female

KW - mice, knockout

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