title: Endogenous IL-13 plays a crucial role in liver granuloma maturation during Leishmania donovani infection, independent of IL-4Rα-responsive macrophages and neutrophils.
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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: McFarlane
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Carter
authors.forename: Andrew N
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: James
authors.initials: J
authors.lastname: Alexander
mesh_terms: D000818:Animals; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D018793:Interleukin-13 / Q000172:deficiency / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D018793:Interleukin-13; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit