IL-4(-/-) mice with lethal Mesocestoides corti infections--reduced Th2 cytokines and alternatively activated macrophages.
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 IFNgamma and TNFalpha. 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.
O'Connell
A E
AE
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Kerepesi
L A
LA
Vandergrift
G L
GL
Herbert
D R
DR
VAN Winkle
T J
TJ
Hooper
D C
DC
Pearce
E J
EJ
Abraham
D
D
D000818:Animals; D002590:Cestode Infections / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008645:Mesocestoides; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma