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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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The L. donovani liver (A), spleen (B), and bone marrow (C) parasite burdens at days 14 and 35 postinfection following intravenous infection with 1–2 × 107 amastigotes. The data are means ± standard errors for individual mice (n = 4) and are representative of 1 of 4 independent experiments.
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fig1: The L. donovani liver (A), spleen (B), and bone marrow (C) parasite burdens at days 14 and 35 postinfection following intravenous infection with 1–2 × 107 amastigotes. The data are means ± standard errors for individual mice (n = 4) and are representative of 1 of 4 independent experiments.

Mentions: Parasite burdens in the livers of wild-type and IL-13-/- BALB/c mice infected intraveneously with 1–2 × 107 L. donovani amastigotes were enumerated at days 14 and 35 postinfection. At day 14 postinfection, liver parasite burdens were similar in both wild-type and IL-13-/- BALB/c mice (Figure 1A). Whereas parasite burdens in the livers of wild-type mice had declined by day 35 postinfection, they did not decline over this period in IL-13-/- BALB/c mice, and we found them to be significantly higher (P < .001) in IL-13-/- than in wild-type mice at this time (Figure 1A). Parasite numbers were also found to be significantly greater in the spleens and bone marrow of L. donovani–infected IL-13-/- compared with those found in wild-type BALB/c mice (Figures 1B and C).


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)

The L. donovani liver (A), spleen (B), and bone marrow (C) parasite burdens at days 14 and 35 postinfection following intravenous infection with 1–2 × 107 amastigotes. The data are means ± standard errors for individual mice (n = 4) and are representative of 1 of 4 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: The L. donovani liver (A), spleen (B), and bone marrow (C) parasite burdens at days 14 and 35 postinfection following intravenous infection with 1–2 × 107 amastigotes. The data are means ± standard errors for individual mice (n = 4) and are representative of 1 of 4 independent experiments.
Mentions: Parasite burdens in the livers of wild-type and IL-13-/- BALB/c mice infected intraveneously with 1–2 × 107 L. donovani amastigotes were enumerated at days 14 and 35 postinfection. At day 14 postinfection, liver parasite burdens were similar in both wild-type and IL-13-/- BALB/c mice (Figure 1A). Whereas parasite burdens in the livers of wild-type mice had declined by day 35 postinfection, they did not decline over this period in IL-13-/- BALB/c mice, and we found them to be significantly higher (P < .001) in IL-13-/- than in wild-type mice at this time (Figure 1A). Parasite numbers were also found to be significantly greater in the spleens and bone marrow of L. donovani–infected IL-13-/- compared with those found in wild-type BALB/c mice (Figures 1B and C).

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