Purpose of Review
Despite over a third of the world’s population being chronically infected with Toxoplasma gondii, little is known about this largely asymptomatic phase of infection. This stage is mediated in vivo by bradyzoites within tissue cysts. The absence of overt symptoms has been attributed to the dormancy of bradyzoites. In this review, we reexamine the conventional view of chronic toxoplasmosis in light of emerging evidence challenging both the nature of dormancy and the consequences of infection in the CNS.
New and emerging data reveal a previously unrecognized level of physiological and replicative capacity of bradyzoites within tissue cysts. These findings have emerged in the context of a reexamination of the chronic infection in the brain that correlates with changes in neuronal architecture, neurochemistry, and behavior that suggest that the chronic infection is not without consequence.
The emerging data driven by the development of new approaches to study the progression of chronic toxoplasma infection reveals significant physiological and replicative capacity for what has been viewed as a dormant state. The emergence of bradyzoite and tissue cyst biology from what was viewed as a physiological “black box” offers exciting new areas for investigation with direct implications on the approaches to drug development targeting this drug-refractory state. In addition, new insights from studies on the neurobiology on chronic infection reveal a complex and dynamic interplay between the parasite, brain microenvironment, and the immune response that results in the detente that promotes the life-long persistence of the parasite in the host.
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Preparation of this article was supported in part by NIH/NIAID R21AI122894 awarded to APS and IDeA award from NIH/NIGMS 5P30GM110787 (COBRE for the Center for Molecular Medicine. PI Louis B Hersh, University of Kentucky) project awarded jointly to APS and MSG.
Conflict of Interest
Matthew Gentry, Anthony Sinai, Animesh Dhara, Elizabeth Watts, Abhijit Patwardhan, and Robert Murphy declare that they have no conflicts of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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Sinai, A.P., Watts, E.A., Dhara, A. et al. Reexamining Chronic Toxoplasma gondii Infection: Surprising Activity for a “Dormant” Parasite. Curr Clin Micro Rpt 3, 175–185 (2016). https://doi.org/10.1007/s40588-016-0045-3
- Tissue cyst
- CNS infection