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

The mean suppression (±standard error) of liver parasite burdens and granuloma induction in the livers of wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox) mice at day 40 postinfection. These are representative data from 2 independent experiments: liver parasite burdens (A), and granuloma maturation in control (B) and drug-treated (C) L. donovani–infected IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice at day 40 postinfection. Mice were treated with phosphate-buffered saline (controls) or 111mg Sbv/kg sodium stibogluconate at days 14 and 15 postinfection. A significant increase in sterile granulomas was observed between control and drug-treated mice with P < .01 and P < .001 for IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice, respectively. *P < .05 drug-treated wild-type (IL-4Rα-/lox) versus drug-treated macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: The mean suppression (±standard error) of liver parasite burdens and granuloma induction in the livers of wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox) mice at day 40 postinfection. These are representative data from 2 independent experiments: liver parasite burdens (A), and granuloma maturation in control (B) and drug-treated (C) L. donovani–infected IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice at day 40 postinfection. Mice were treated with phosphate-buffered saline (controls) or 111mg Sbv/kg sodium stibogluconate at days 14 and 15 postinfection. A significant increase in sterile granulomas was observed between control and drug-treated mice with P < .01 and P < .001 for IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice, respectively. *P < .05 drug-treated wild-type (IL-4Rα-/lox) versus drug-treated macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox).

Mentions: SSG drug-induced suppression of parasite burdens in the liver was equivalent in control (59%) and macrophage/neutrophil-specific IL-4Rα-/- (55%) mice at day 40 postinfection (Figure 6A), indicating that treatment was successful in both mouse strains. In agreement, compared with non-drug-treated mice (Figure 6B), both drug-treated control mice and macrophage/neutrophil-specific IL-4Rα-/- mice (Figure 6C) showed a significant increase (P < .01 and P < .001 respectively) in sterile granulomas (Figure 6B).


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 mean suppression (±standard error) of liver parasite burdens and granuloma induction in the livers of wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox) mice at day 40 postinfection. These are representative data from 2 independent experiments: liver parasite burdens (A), and granuloma maturation in control (B) and drug-treated (C) L. donovani–infected IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice at day 40 postinfection. Mice were treated with phosphate-buffered saline (controls) or 111mg Sbv/kg sodium stibogluconate at days 14 and 15 postinfection. A significant increase in sterile granulomas was observed between control and drug-treated mice with P < .01 and P < .001 for IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice, respectively. *P < .05 drug-treated wild-type (IL-4Rα-/lox) versus drug-treated macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: The mean suppression (±standard error) of liver parasite burdens and granuloma induction in the livers of wild-type (IL-4Rα-/lox) and macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox) mice at day 40 postinfection. These are representative data from 2 independent experiments: liver parasite burdens (A), and granuloma maturation in control (B) and drug-treated (C) L. donovani–infected IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice at day 40 postinfection. Mice were treated with phosphate-buffered saline (controls) or 111mg Sbv/kg sodium stibogluconate at days 14 and 15 postinfection. A significant increase in sterile granulomas was observed between control and drug-treated mice with P < .01 and P < .001 for IL-4Rα-/lox and LysMcreIL-4Rα-/lox mice, respectively. *P < .05 drug-treated wild-type (IL-4Rα-/lox) versus drug-treated macrophage/neutrophil-specific IL-4Rα-/- (LysMcreIL-4Rα-/lox).
Mentions: SSG drug-induced suppression of parasite burdens in the liver was equivalent in control (59%) and macrophage/neutrophil-specific IL-4Rα-/- (55%) mice at day 40 postinfection (Figure 6A), indicating that treatment was successful in both mouse strains. In agreement, compared with non-drug-treated mice (Figure 6B), both drug-treated control mice and macrophage/neutrophil-specific IL-4Rα-/- mice (Figure 6C) showed a significant increase (P < .01 and P < .001 respectively) in sterile granulomas (Figure 6B).

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