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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

cd8 t cells

Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer

September 3, 2017
Ngo, H. M., Zhou, Y., Lorenzi, H., Wang, K., Kim, T. K., Zhou, Y., El Bissati, K., Mui, E., Fraczek, L., Rajagopala, S. V., Roberts, C. W., Henriquez, F. L., Montpetit, A., Blackwell, J. M., Jamieson, S. E., Wheeler, K., Begeman, I. J., Naranjo-Galvis, C., Alliey-Rodriguez, N., Davis, R. G., Soroceanu, L., Cobbs, C., Steindler, D. A., Boyer, K., Noble, A. G., Swisher, C. N., Heydemann, P. T., Rabiah, P., Withers, S., Soteropoulos, P., Hood, L., McLeod, R.
Scientific Reports 2017; 7: doi:10.1038/s41598-017-10675-6
Click for abstract
One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases.

Tagged: adult human brain, alzheimers-disease, cd8 t cells, fibroblast-growth-factor, genome-wide association, kappa-b aktivity, neural progenitor cells, protein interaction networks, receptor gene oxtr, virulence factor rop18

Mental healthPhysical health

Psychiatric disorders in Toxoplasma seropositive patients – CD8 connection

October 11, 2013 11 Comments
Bhadra, R., Cobb, D. A., Weiss, L. M., Khan, I. A.
Schizophrenia Bulletin 2013; 39: 485-489
Click for abstract
Although the highest numbers of studies linking an infectious agent with schizophrenia has involved the parasite Toxoplasma gondii, the mechanistic underpinnings of this correlation has remained unaddressed. Incidentally, CD8 T cells, which play a pivotal role in mediating long-term immunity to Toxoplasma, are downregulated in schizophrenia patients. Recent studies have demonstrated that CD8 response is also impaired during chronic toxoplasmosis in murine models. In light of these new findings, in this article, we discuss the potential role of CD8 T cells in causing altered mental status in Toxoplasma seropositive schizophrenia patients.

Tagged: behavior, cd8 t cells, cells, disease, Dopamine, exhaustion, gondii, infection, lymphocytes, oxoplasma, pd-1, receptors, risk factors, Schizophrenia

Mental health

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