Reexamining Chronic Toxoplasma gondii Infection: Surprising Activity for a “Dormant” Parasite

Abstract

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. Recent Findings 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. Summary 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.

A single-parasite transcriptional atlas of Toxoplasma Gondii reveals novel control of antigen expression

“…Interestingly, bradyzoites are found predominantly in G 1 b but not in G 1 a, suggesting the possibility of a putative checkpoint between these two phases that may also play a role in regulating the developmental transition. Our data further shows a small fraction of bradyzoites to be cycling which supports the hypothesis that bradyzoites can in fact divide 22 . Our results showed a very strong correlation between cell cycle and expression of genes encoding proteins in various subcellular organelles, as noted previously using synchronized bulk populations 28 .…”

“…Furthermore, parasites within the same tissue cysts have been shown to display heterogeneity in the expression of bradyzoite marker proteins 20 . The transition of tachyzoites to the bradyzoite stage results in an overwhelming majority of mature bradyzoites in the G 1 phase of the cell cycle that divide slowly, if at all 21,22 . Furthermore, tachyzoites exhibit slower growth kinetics immediately prior to the bradyzoite transition 21,23 .…”

CSF in acute and chronic infectious diseases

“…Toxoplasmosis is caused by Toxoplasma gondii, which develops into cysts in muscles (skeletal and cardiac), retina, and the brain. The infection itself is often (Brooks et al, 2015;Ngoungou et al, 2015;Cabral et al, 2016;Sinai et al, 2016). Clinical manifestation in echinococcosis can be quite variable depending on the strain: cystic echinococcosis is caused by Echinococcus granulosus, while alveolar echinococcosis is caused by E. multilocularis.…”

Evidence of increased exposure to Toxoplasma gondii in individuals with recent onset psychosis but not with established schizophrenia

“…Previously, tissue cysts were not thought to cause symptoms in immune competent hosts. However recently studies have documented that tissue cysts are engaged in active metabolism and interaction with the host [ 1 ]. Accordingly, serological studies indicate that exposure to Toxoplasma can be associated with eye disease [ 2 ] as well as an increased risk of a range of neuropsychiatric diseases including schizophrenia[ 3 , 4 ], bipolar disorder[ 5 ], suicidal behavior[ 6 ], anxiety disorder [ 7 ] and cognitive decline in the elderly [ 8 ] in some populations.…”