One-third of humans are infected lifelong with the brain-dwelling, protozoan parasite Toxoplasma gondii. This parasite completes one stage of its life-cycle in cats and spreads to humans from cat faeces. It is also transmitted from mother to child during pregnancy if the mother is infected (congenital toxoplasmosis) or via undercooked meat.
While the infection is asymptomatic in most humans, it can cause severe problems in those who have compromised immune systems.
The parasitic infection is also associated with abnormal behaviors in infected rats, causing aberrations in their olfactory sense, so much so, that the rodents’ fear of cats is removed.
Interestingly, the Toxoplasma parasite has also been correlated with behavioral impairment and neurological disorders in humans. However, it was difficult to reach a consensus from correlation and epidemiological studies, due to lack of direct evidence of molecular mechanisms.
Now, a study published in the open access journal Scientific Reports shows that the parasite modulates pathways related to epilepsy, Parkinson’s, Alzheimer’s disease and also cancer.
Researchers from 16 institutions across the U.S., Canada, England, Scotland, and Australia analyzed genetic data from a unique cohort of infected individuals, to identify susceptibility genes to pathogenic infections, and brain-disease associated markers.
In addition, transcriptomic and proteomic data from cell culture studies was analyzed to study the effect of Toxoplasma infections at the molecular level.
The data was finally mined to study host and parasite interactions. A systems biology approach was adopted to associate neural protein network perturbations with parasitic molecules. The results demonstrated that the Toxoplasma parasite modulates a number of regulatory proteins that are associated with neurological diseases. The study also showed largest perturbations of cancer-related protein networks.
“This study is a paradigm shifter,” says study co-author Dr. Dennis Steindler, a neuroscientist and aging expert at Tufts University.
“We now have to insert infectious disease into the equation of neurodegenerative diseases, epilepsy and neural cancers.”
While this is troubling, further analysis and research are required to study various aspects of how a parasitic infection perturbs specific host signaling pathways. Specifically, the parasite in itself may not cause neurological disorders but influences pre-existing conditions to affect the final disease prognosis.
“As a number of proteins and networks are involved, the prognosis may be affected by other factors such as- “pregnancy, stress, other infections, and a deficient microbiome,” said lead author Dr. Rima McLeod, medical director of the Toxoplasmosis Center at the University of Chicago.
The researchers collected and analyzed data from the National Collaborative Chicago-Based Congenital Toxoplasmosis Study, which has studied and treated 246 people with congenital toxoplasmosis since 1981.
The results showed that fragments of microRNA and proteins found in children with severe toxoplasmosis matched up with biomarkers found in patients with a range of neurodegenerative conditions, including Alzheimer’s and Parkinson’s.
The study provides a comprehensive and integrated model of development of brain diseases from toxoplasmosis. It also highlights the necessity of considering parasitic and other pathogenic infections as important factors in the prognosis of complex multifactorial diseases, such as neurological disorders and cancer.
The challenge will be to design relevant treatments and prevention strategies.
“We have to translate aspects of this study into preventive treatments that include everything from drugs to diet to lifestyle, in order to delay disease onset and progression,” concluded Dr. Steindler.
The study may be accessed here.