A common parasite in the brain is far more active than we thought

People most often contract toxoplasmosis by eating undercooked meat or coming into contact with contaminated soil or cat feces. Once inside the body, the parasite is known for its ability to evade detection by forming microscopic cysts, primarily in the brain and muscle tissue.

In most cases, infected individuals never experience noticeable symptoms. Even so, the parasite stays in the body for life, sealed inside cysts that can contain hundreds of parasites. These dormant forms can become active again later, especially in people with weakened immune systems, sometimes leading to serious complications involving the brain or eyes. Infection during pregnancy poses additional risks, as it can cause severe health problems for developing babies with immature immune systems.

Cysts Are Not as Simple as Once Thought

For many years, scientists assumed that each cyst housed a single, uniform type of parasite that remained inactive until it reawakened. Using advanced single-cell analysis, the UC Riverside team found that this assumption was wrong. Their research shows that every cyst contains multiple parasite subtypes, each performing different biological functions.

“We found the cyst is not just a quiet hiding place — it’s an active hub with different parasite types geared toward survival, spread, or reactivation,” said Emma Wilson, a professor of biomedical sciences in the UCR School of Medicine and lead author of the study.

Inside the Structure of Toxoplasma Cysts

Wilson explained that cysts develop gradually as the immune system applies pressure on the parasite. Each cyst is surrounded by a protective wall and packed with hundreds of slow-growing parasites known as bradyzoites. While cysts are microscopic, they are relatively large compared to other intracellular pathogens, reaching up to 80 microns across. Individual bradyzoites measure about five microns in length.

These cysts are most commonly found in neurons, but they also appear frequently in skeletal and cardiac muscle. This detail is especially important because humans are often infected by eating undercooked meat that contains these cysts.

Why Cysts Matter for Disease and Treatment

According to Wilson, cysts play a central role in both disease progression and transmission. Once formed, they resist all current therapies and persist in the body indefinitely. They also help the parasite spread between hosts.

When cysts reactivate, bradyzoites transform into rapidly multiplying tachyzoites that move throughout the body. This process can lead to severe illnesses such as toxoplasmic encephalitis (neurological damage) or retinal toxoplasmosis (vision loss).

Rethinking the Toxoplasma Life Cycle

“For decades, the Toxoplasma life cycle was understood in overly simplistic terms, conceptualized as a linear transition between tachyzoite and bradyzoite stages,” Wilson said. “Our research challenges that model. By applying single-cell RNA sequencing to parasites isolated directly from cysts in vivo, we found unexpected complexity within the cyst itself. Rather than a uniform population, cysts contain at least five distinct subtypes of bradyzoites. Although all are classified as bradyzoites, they are functionally different, with specific subsets primed for reactivation and disease.”

Overcoming Longstanding Research Barriers

Studying cysts has historically been difficult. They develop slowly, are deeply embedded in tissues like the brain, and do not form efficiently in standard lab cultures. Because of these challenges, most past research has focused on tachyzoites grown in vitro, leaving the biology of cyst-dwelling bradyzoites largely unexplored.

“Our work overcomes those limitations by using a mouse model that closely mirrors natural infection,” Wilson said. “Because mice are a natural intermediate host for Toxoplasma, their brains can harbor thousands of cysts. By isolating these cysts, digesting them enzymatically, and analyzing individual parasites, we were able to gain a view of chronic infection as it occurs in living tissue.”

Implications for Future Treatments

Wilson noted that while current medications can control the fast-growing form of the parasite responsible for acute illness, they cannot eliminate cysts.

“By identifying different parasite subtypes inside cysts, our study pinpoints which ones are most likely to reactivate and cause damage,” she said. “This helps explain why past drug development efforts have struggled and suggests new, more precise targets for future therapies.”

Ongoing Risks and a Shift in Focus

Congenital toxoplasmosis remains a serious concern when infection occurs for the first time during pregnancy, as it can result in severe fetal complications. Although prior immunity usually protects the fetus, routine screening is not available in some countries, highlighting the challenges of managing an infection that is widespread but often symptom-free.

Despite how common toxoplasmosis is, it has received far less attention than many other infectious diseases. Wilson hopes the findings will help change that.

“Our work changes how we think about the Toxoplasma cyst,” she said. “It reframes the cyst as the central control point of the parasite’s life cycle. It shows us where to aim new treatments. If we want to really treat toxoplasmosis, the cyst is the place to focus.”

Study Details and Funding

Wilson conducted the study alongside Arzu Ulu, Sandeep Srivastava, Nala Kachour, Brandon H. Le, and Michael W. White. Wilson and White are co-corresponding authors.

The research was funded by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The paper is titled “Bradyzoite subtypes rule the crossroads of Toxoplasma development.”