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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.

McFarlane E, Carter KC, McKenzie AN, Kaye PM, Brombacher F, Alexander J - J. Infect. Dis. (2011)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.

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.

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Related in: MedlinePlus

Liver parasite burdens in wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- BALB/c (LysMcreIL-4Rα-/lox) mice at day 40 postinfection with 1–2 × 107 L. donovani amastigotes. Part A shows representative data from 3 independent experiments. Parts B and C are light micrographs from an IL-4Rα-/lox mouse and a LysMcreIL-4Rα-/lox mouse, respectively, at day 40 postinfection; they show mature granulomas (arrows) consisting of well-developed mononuclear cell mantles (magnification 400x).
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fig5: Liver parasite burdens in wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- BALB/c (LysMcreIL-4Rα-/lox) mice at day 40 postinfection with 1–2 × 107 L. donovani amastigotes. Part A shows representative data from 3 independent experiments. Parts B and C are light micrographs from an IL-4Rα-/lox mouse and a LysMcreIL-4Rα-/lox mouse, respectively, at day 40 postinfection; they show mature granulomas (arrows) consisting of well-developed mononuclear cell mantles (magnification 400x).

Mentions: Primary infection of macrophage/neutrophil-specific IL-4Rα-/- mice (LysMcreIL-4Rα-/lox) and their control littermates (IL-4Rα-/lox) with L. donovani resulted in similar liver parasite burdens (Figure 5A) and granuloma maturation (Figures 5B and 5C). As previously published, global IL-4Rα-/- BALB/c mice were more susceptible to infection than wild-type mice and have retarded granuloma development [4] with a histological phenotype similar to IL-13-/- animals (results not shown).


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

McFarlane E, Carter KC, McKenzie AN, Kaye PM, Brombacher F, Alexander J - J. Infect. Dis. (2011)

Liver parasite burdens in wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- BALB/c (LysMcreIL-4Rα-/lox) mice at day 40 postinfection with 1–2 × 107 L. donovani amastigotes. Part A shows representative data from 3 independent experiments. Parts B and C are light micrographs from an IL-4Rα-/lox mouse and a LysMcreIL-4Rα-/lox mouse, respectively, at day 40 postinfection; they show mature granulomas (arrows) consisting of well-developed mononuclear cell mantles (magnification 400x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105032&req=5

fig5: Liver parasite burdens in wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- BALB/c (LysMcreIL-4Rα-/lox) mice at day 40 postinfection with 1–2 × 107 L. donovani amastigotes. Part A shows representative data from 3 independent experiments. Parts B and C are light micrographs from an IL-4Rα-/lox mouse and a LysMcreIL-4Rα-/lox mouse, respectively, at day 40 postinfection; they show mature granulomas (arrows) consisting of well-developed mononuclear cell mantles (magnification 400x).
Mentions: Primary infection of macrophage/neutrophil-specific IL-4Rα-/- mice (LysMcreIL-4Rα-/lox) and their control littermates (IL-4Rα-/lox) with L. donovani resulted in similar liver parasite burdens (Figure 5A) and granuloma maturation (Figures 5B and 5C). As previously published, global IL-4Rα-/- BALB/c mice were more susceptible to infection than wild-type mice and have retarded granuloma development [4] with a histological phenotype similar to IL-13-/- animals (results not shown).

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.

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.

Show MeSH
Related in: MedlinePlus