Interleukin-12 promotes pathologic liver changes and death in mice coinfected with Schistosoma mansoni and Toxoplasma gondii.
We previously demonstrated that mice concurrently infected with Schistosoma mansoni and Toxoplasma gondii undergo accelerated mortality which is preceded by severe liver damage. Abnormally high levels of serum tumor necrosis factor alpha (TNF-alpha) in the dually infected mice suggested a role for this and related proinflammatory mediators in the pathologic alterations. In order to evaluate the factors involved in increased inflammatory-mediator production and mortality, interleukin-12(-/-) (IL-12(-/-)) mice were coinfected with S. mansoni and T. gondii, and survival and immune responses were monitored. These IL-12(-/-) mice displayed decreased liver damage and prolonged time to death relative to wild-type animals also coinfected with these parasites. Relative to the response of cells from the coinfected wild-type animals, levels of TNF-alpha, gamma interferon, and NO produced by splenocytes from coinfected IL-12(-/-) mice were reduced, and levels of IL-5 and IL-10 were increased, with the net result that the immune response of the dually infected IL-12(-/-) mice was similar to that of the wild-type mice infected with S. mansoni alone. While dually infected wild-type animals succumb in the absence of overt parasitemia, the delayed death in the absence of IL-12 is associated with relatively uncontrolled T. gondii replication. These data support the view that S. mansoni-infected mice are acutely sensitive to infection with T. gondii as a result of their increased hepatic sensitivity to high levels of proinflammatory cytokines; IL-12 and TNF-alpha are implicated in this process.
Araujo
M I
MI
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Bliss
S K
SK
Suzuki
Y
Y
Alcaraz
A
A
Denkers
E Y
EY
Pearce
E J
EJ
D000818:Animals; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D012555:Schistosomiasis mansoni / Q000150:complications* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D017741:Survivors; D018418:Th2 Cells; D014124:Toxoplasmosis, Animal / Q000150:complications* / Q000276:immunology / Q000401:mortality / Q000473:pathology
D018836:Inflammation Mediators; D018664:Interleukin-12