Murine March Madness: Anatomical analysis of infection in the brain
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The location of Toxoplasma in the brain, the chronicity of infection and the role of inflammatory mediators has led to speculation as to the changes caused by chronic, yet subclinical, infection in the brain. Our own studies and others have demonstrated significant infection-induced changes in neurotransmitters; however, the molecular basis or the downstream consequences of these changes are not understood.
Here we present a wide-ranging study on NanoString analysis of Toxoplasma-induced changes in RNA and protein in the infected brain over the course of infection. Using brain samples from infected and uninfected mice, genes associated with neuropathology and neuroinflammation were probed while simultaneously measuring a set of genes associated with early and late parasite development. Further, by analyzing a comprehensive protein panel in specific areas of the brain including the meninges, choroid plexus and vasculature and directly around Toxoplasma cysts, we confirm many published data on Toxoplasma-induced neurological changes and reveal novel and significant biology on the balance of having a parasite in your brain.
For Research Use Only. Not for Use in Diagnostic Procedures.
Emma Wilson, PhD
Associate Dean of Graduate Division, Professor of Biomedical Sciences
University of California, Riverside
The primary focus of the lab is the immune response in the brain following Toxoplasma gondii infection. This is a common parasitic infection of many mammals including humans where prevalence is 10-30% in the USA and up to 80% in parts of Europe and South America. Infection with this parasite leads to an acute systemic inflammatory response that is controlled resulting in a chronic phase of infection where the parasite is maintained predominantly as a slow replicating form in the CNS. In most cases this results in no overt pathology however in the absence of an appropriate immune response, the parasite will reactivate leading to Toxoplasmic encephalitis (TE) a disease that is often fatal if left untreated.
Thus, T. gondii infection is a rare example of a finely tuned immune response in the brain where there is a balance between control of the parasite and immunopathology. Understanding the mechanisms that control this balance may improve our ability to control an inappropriate immune response in the CNS.