IL-4−/− mice with lethal Mesocestoides corti infections – reduced Th2 cytokines and alternatively activated macrophages
A. E. O’CONNELL
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Authors contributed equally to this work.
Search for more papers by this authorL. A. KEREPESI
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Authors contributed equally to this work.
Search for more papers by this authorD. R. HERBERT
Research Service, Cincinnati Veterans Administration Medical Center, Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Search for more papers by this authorT. J. VAN WINKLE
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Search for more papers by this authorD. C. HOOPER
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorE. J. PEARCE
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Search for more papers by this authorD. ABRAHAM
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorA. E. O’CONNELL
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Authors contributed equally to this work.
Search for more papers by this authorL. A. KEREPESI
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Authors contributed equally to this work.
Search for more papers by this authorD. R. HERBERT
Research Service, Cincinnati Veterans Administration Medical Center, Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Search for more papers by this authorT. J. VAN WINKLE
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Search for more papers by this authorD. C. HOOPER
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorE. J. PEARCE
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Search for more papers by this authorD. ABRAHAM
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorDisclosures: None
Summary
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.
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