Toxoplasma gondii and Schistosoma mansoni synergize to promote hepatocyte dysfunction associated with high levels of plasma TNF-alpha and early death in C57BL/6 mice

To address the question of how the murine host responds to a prototypic type 1 cytokine inducer while concurrently undergoing a helminth-induced type 2 cytokine response, C57BL/6 strain animals with patent schistosomiasis mansoni were orally infected with the cystogenic Toxoplasma gondii strain ME49...

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Veröffentlicht in:The Journal of immunology (1950) 1999-08, Vol.163 (4), p.2089-2097
Hauptverfasser: Marshall, A J, Brunet, L R, van Gessel, Y, Alcaraz, A, Bliss, S K, Pearce, E J, Denkers, E Y
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container_issue 4
container_start_page 2089
container_title The Journal of immunology (1950)
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creator Marshall, A J
Brunet, L R
van Gessel, Y
Alcaraz, A
Bliss, S K
Pearce, E J
Denkers, E Y
description To address the question of how the murine host responds to a prototypic type 1 cytokine inducer while concurrently undergoing a helminth-induced type 2 cytokine response, C57BL/6 strain animals with patent schistosomiasis mansoni were orally infected with the cystogenic Toxoplasma gondii strain ME49. Schistosoma mansoni infection resulted in a significantly higher mortality rate when mice were subsequently orally infected with ME49, and these animals displayed a defective IFN-gamma and NO response relative to animals infected with T. gondii alone. Plasma levels of TNF-alpha and aspartate transaminase in double-infected mice were greatly elevated relative to mice infected with either parasite alone. Consistent with the latter observation, these animals exhibited severe liver pathology, with regions of coagulative necrosis and hepatocyte vacuolization unapparent in mice carrying either infection alone. Interestingly, mean egg granuloma size was approximately 50% of that in mice with S. mansoni infection alone. The exacerbated liver pathology in coinfected mice did not appear to be a result of uncontrolled tachyzoite replication, because both parasite-specific RT-PCR analysis and immunohistochemical staining demonstrated a low number of tachyzoites in the liver. We hypothesize that mortality in these animals results from the high level of systemic TNF-alpha, which mediates a severe liver pathology culminating in death of the animal.
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subjects Animals
Disease Susceptibility
Female
Immunoglobulin E - blood
Interferon-gamma - biosynthesis
Interferon-gamma - blood
Intestinal Diseases, Parasitic - pathology
Liver Diseases, Parasitic - immunology
Liver Diseases, Parasitic - mortality
Liver Diseases, Parasitic - parasitology
Liver Diseases, Parasitic - pathology
Mice
Mice, Inbred C57BL
Schistosoma mansoni
Schistosoma mansoni - immunology
Schistosoma mansoni - pathogenicity
Schistosomiasis mansoni - blood
Schistosomiasis mansoni - immunology
Schistosomiasis mansoni - mortality
Schistosomiasis mansoni - pathology
Toxoplasma - growth & development
Toxoplasma - immunology
Toxoplasma - pathogenicity
Toxoplasma gondii
Toxoplasmosis, Animal - immunology
Toxoplasmosis, Animal - mortality
Toxoplasmosis, Animal - parasitology
Toxoplasmosis, Animal - pathology
Tumor Necrosis Factor-alpha - metabolism
title Toxoplasma gondii and Schistosoma mansoni synergize to promote hepatocyte dysfunction associated with high levels of plasma TNF-alpha and early death in C57BL/6 mice
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