Limits...
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.

Show MeSH

Related in: MedlinePlus

Sodium stibogluconate–mediated suppression of parasite burdens in the liver and granuloma maturation in IL-13-/- and wild-type BALB/c mice infected with L. donovani. The mean suppression (± standard error [SE]) of parasite burdens induced by treatment with 111 mg Sbv/kg sodium stibogluconate (SSG) at days 14 and 15 postinfection in the livers of wild-type and IL-13-/- mice was assessed at day 40 postinfection (A). Parasite suppression was measured by comparing each experimental value with the mean control value (NS = no suppression). Granuloma maturation in non–drug-treated (B) and drug-treated (C) L. donovani–infected wild-type and IL-13-/- mice at day 40 postinfection was also measured. Paraffin-embedded liver sections from wild-type and IL-13-/- mice (n = 4) were stained with haematoxylin and eosin, and granuloma formation per 100 microscopic fields was determined. The data are means (±SE) for 1 of 2 independent experiments. **P < .01 wild-type versus IL-13-/-.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3105032&req=5

fig4: Sodium stibogluconate–mediated suppression of parasite burdens in the liver and granuloma maturation in IL-13-/- and wild-type BALB/c mice infected with L. donovani. The mean suppression (± standard error [SE]) of parasite burdens induced by treatment with 111 mg Sbv/kg sodium stibogluconate (SSG) at days 14 and 15 postinfection in the livers of wild-type and IL-13-/- mice was assessed at day 40 postinfection (A). Parasite suppression was measured by comparing each experimental value with the mean control value (NS = no suppression). Granuloma maturation in non–drug-treated (B) and drug-treated (C) L. donovani–infected wild-type and IL-13-/- mice at day 40 postinfection was also measured. Paraffin-embedded liver sections from wild-type and IL-13-/- mice (n = 4) were stained with haematoxylin and eosin, and granuloma formation per 100 microscopic fields was determined. The data are means (±SE) for 1 of 2 independent experiments. **P < .01 wild-type versus IL-13-/-.

Mentions: We treated L. donovani–infected wild-type and IL-13-/- BALB/c mice with SSG (111 mg Sbv/Kg) on days 14 and 15 postinfection, and we compared parasite burdens with those of non–drug-treated control mice at day 40 postinfection. We calculated SSG parasite suppression by comparing each experimental value with the mean control value. As expected, SSG drug treatment was successful in wild-type animals, resulting in 61% suppression of parasite numbers in the liver (Figure 4A). Interestingly, SSG drug treatment was ineffective in IL-13-/- mice, as parasite burdens at day 40 postinfection were similar to control values.


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)

Sodium stibogluconate–mediated suppression of parasite burdens in the liver and granuloma maturation in IL-13-/- and wild-type BALB/c mice infected with L. donovani. The mean suppression (± standard error [SE]) of parasite burdens induced by treatment with 111 mg Sbv/kg sodium stibogluconate (SSG) at days 14 and 15 postinfection in the livers of wild-type and IL-13-/- mice was assessed at day 40 postinfection (A). Parasite suppression was measured by comparing each experimental value with the mean control value (NS = no suppression). Granuloma maturation in non–drug-treated (B) and drug-treated (C) L. donovani–infected wild-type and IL-13-/- mice at day 40 postinfection was also measured. Paraffin-embedded liver sections from wild-type and IL-13-/- mice (n = 4) were stained with haematoxylin and eosin, and granuloma formation per 100 microscopic fields was determined. The data are means (±SE) for 1 of 2 independent experiments. **P < .01 wild-type versus IL-13-/-.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Sodium stibogluconate–mediated suppression of parasite burdens in the liver and granuloma maturation in IL-13-/- and wild-type BALB/c mice infected with L. donovani. The mean suppression (± standard error [SE]) of parasite burdens induced by treatment with 111 mg Sbv/kg sodium stibogluconate (SSG) at days 14 and 15 postinfection in the livers of wild-type and IL-13-/- mice was assessed at day 40 postinfection (A). Parasite suppression was measured by comparing each experimental value with the mean control value (NS = no suppression). Granuloma maturation in non–drug-treated (B) and drug-treated (C) L. donovani–infected wild-type and IL-13-/- mice at day 40 postinfection was also measured. Paraffin-embedded liver sections from wild-type and IL-13-/- mice (n = 4) were stained with haematoxylin and eosin, and granuloma formation per 100 microscopic fields was determined. The data are means (±SE) for 1 of 2 independent experiments. **P < .01 wild-type versus IL-13-/-.
Mentions: We treated L. donovani–infected wild-type and IL-13-/- BALB/c mice with SSG (111 mg Sbv/Kg) on days 14 and 15 postinfection, and we compared parasite burdens with those of non–drug-treated control mice at day 40 postinfection. We calculated SSG parasite suppression by comparing each experimental value with the mean control value. As expected, SSG drug treatment was successful in wild-type animals, resulting in 61% suppression of parasite numbers in the liver (Figure 4A). Interestingly, SSG drug treatment was ineffective in IL-13-/- mice, as parasite burdens at day 40 postinfection were similar to control values.

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