IL-4⁻/⁻ mice with lethal Mesocestoides corti infections - reduced Th2 cytokines and alternatively activated macrophages

• Published in: Parasite immunology Vol. 31; no. 12; pp. 741 - 749
• Main Authors: O'CONNELL, A.E, KEREPESI, L.A, VANDERGRIFT, G.L, HERBERT, D.R, VAN WINKLE, T.J, HOOPER, D.C, PEARCE, E.J, ABRAHAM, D
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.12.2009; Blackwell Publishing Ltd
• Subjects: alternatively activated macrophages; Animals; Cestode Infections - immunology; Cestode Infections - metabolism; Cestode Infections - parasitology; classically activated macrophages; Host-Parasite Interactions - immunology; Host-Parasite Interactions - physiology; Interferon-gamma - biosynthesis; interleukin-4; Interleukin-4 - genetics; Interleukin-4 - immunology; Interleukin-5 - biosynthesis; Liver - immunology; Liver - parasitology; Macrophage Activation; Macrophages - immunology; Mesocestoides; Mesocestoides corti; Mice; Mice, Inbred BALB C; Mice, Knockout; Spleen - immunology; Spleen - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0141-9838; 1365-3024
• DOI: 10.1111/j.1365-3024.2009.01151.x

Protection against Mesocestoides corti, a cestode that invades vital organs, is dependent on the production of IL-4, as IL-4⁻/⁻ mice were found to have higher parasite burdens when compared with wild-type mice. The goal of this study was to investigate the role of IL-4 in immunity to M. corti, focusing on the immunological profile and on potential mediators of pathology. IL-4⁻/⁻ mice infected with M. corti showed 100% mortality by 32 days, whereas wild-type mice survived for approximately 1 year. Parasite burdens were significantly increased in the liver, peritoneal, and thoracic cavities of IL-4⁻/⁻ mice, associated with impaired recruitment of inflammatory cells and a reduction in monocytes and macrophages. IL-5 production by splenocytes and expression in liver tissue was decreased in infected IL-4⁻/⁻ mice compared with wild-type mice. In contrast, IL-4⁻/⁻ mice produced increased amounts of IFNγ and TNFα. Alternatively activated macrophages were a major feature of liver granulomas in wild-type mice evidenced by Arginase I expression, while livers from infected IL-4⁻/⁻ mice showed impaired alternative macrophage activation without increased classical macrophage activation. Thus, lethality during M. corti infection of IL-4⁻/⁻ mice is associated with decreased Th2 cytokines, increased Th1 cytokines and impairment of alternatively activated macrophages.