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Neurotoxicity and Immunotoxicity Assessment in CBA/J Mice with Chronic Toxoplasma gondii Infection and Single-Dose Exposure to Methylmercury

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA

David S. Lindsay

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA

Steven Holladay

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA

Marion Ehrich

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA

Toxoplasma gondii is a protozoan parasite that localizes in the brain where it can cause life-threatening disease. Methylmercury (Me Hg) is a well-documented neurotoxicant that accumulates in the brain. We investigated end points associated with immunotoxicity and neurotoxicity in mice exposed to Me Hg during a chronic T. gondii infection. Two groups of 6-week-old, female CBA/J mice were either fed 25 T. gondii tissue cysts of the ME-49 strain or given vehicle. Six weeks later, half of the mice in each group were orally gavaged with a single dose of 20 mg/kg body weight of Me Hg, creating four groups of mice (vehicle control, T. gondii, Me Hg, and T. gondii/Me Hg). Mice were sacrificed 7 days post Me Hg exposure. Me Hg exposure caused a significant decrease in mouse body weight. Me Hg administration resulted in an increase of splenic cellularity and spleen-to-body weight ratios. Me Hg had no significant effect on the percentages of CD4⁺, CD8⁺, or non-T-cell subpopulations in the spleen. Me Hg dosed mice demonstrated an increase in absolute numbers of splenic CD4⁺, CD8⁺, or non-T cells when compared to mice in control and T. gondii-infected groups. Thymic CD4⁺CD8⁺ T-cell subpopulations were decreased (p <.05) by Me Hg with or without a concurrent T. gondii infection. There was a significant (p <.05) increase in brain tissue cyst counts within the group exposed to both Me Hg and T. gondii (16 4, mean SE, n = 7) versus T. gondii alone (4 1, n = 8). Histopathological examination demonstrated encephalitis, gliosis, and meningitis in brains from mice infected with T. gondii. These data indicate that exposure to both Me Hg and T. gondii has synergistic effects, with effects of Me Hg especially on the immune system.

Key Words: CBA/J Mice • Environmental Contaminants • Immunotoxicity • Methylmercury • T-Cell Subsets • T. gondii

International Journal of Toxicology, Vol. 22, No. 1, 53-61 (2003)
DOI: 10.1080/10915810305075


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