A new grant from NIH will fund CPP Research to find out how the immune system combats this common parasitic infection, potentially leading the way to better treatment. Assistant Professor Tatiane Lima is the Principal Investigator on the grant.
Lima began researching the parasite Toxoplasma gondii as a postdoc at UCI and has pursued the work at CPP, providing students with exceptional opportunities for biomedical research. While 12% of the U.S. population has this parasite in their bodies, Lima shared that in her native country of Brazil 60% or more have been infected. The rate of adults testing positive in France is about 50%.
The disease is not transmitted person to person, except during pregnancy, which can result in blindness, miscarriage, or stillbirth. Cats are the definitive hosts of the parasite T. gondii. Oocysts from the parasite are shed in the cat’s feces and is spread through contact with it. Contamination can occur in soil, water, or food. All warm-blooded animals can host the parasite so undercooked livestock is also a potential source.
In humans, the acute phase (early infection) may cause flu-like symptoms. In the chronic phase most humans with a healthy immune system won’t exhibit symptoms which is probably why, in spite of its prevalence, it’s understudied, and seldom mentioned. However, the parasite can lie dormant in the body and reactivate when the immune system is compromised.
What makes the parasite so problematic is that it’s intracellular and can reside in the cells of vital organs like the brain, heart, and lungs. Though the body mounts an immune response that can keep it in check, it has ways to survive that include manipulating host cell pathways and creating a parasitophorous vacuole that protects it from the host cell.
“Neutrophils and monocytes (two types of white blood cells) are the first to respond to the infection. If we can enhance that response, we can limit the replication of the parasite so it doesn’t spread,” Lima said. “We need to understand the early immune response.”
Neutrophils are infected with the parasite through cell invasion or phagocytosis. Lima and her students will study the formation of reactive oxygen species (ROS) which plays a role in the creation of neutrophil extracellular traps (NETs). NETs are made when the cell releases DNA and toxic proteins that can kill T. gondii. The research will identify the cellular events that induce ROS, pointing the way to how it might be enhanced.
“We’ll use CRISPR to knock out receptors and intracellular molecules to determine which are causing the production of ROS,” Lima said. She currently has two graduate students and two undergrads working on this project. The research will provide opportunities for 4-6 grad students who will each work with 1-2 undergrads.
“What interests me about the research is having the opportunity to discover the answers to these scientific questions,” graduate student Anthony Temm said. “I would like to continue as a researcher and one day be in charge of my own team and this experience is preparing me for that by teaching me lab techniques and how to teach others.”
“I transferred to CPP as a biotechnology major to expand my opportunities,” senior Lynne Payad said. “The research has taught me skills in the lab and given me confidence outside of it, leading me toward considering graduate studies.”
It’s estimated that two billion people worldwide have this parasite in their brain. Venjaminne Fua,one of Lima’s graduate students, is studying the neurological effects of the disease for his master’s thesis. A Medscape article cites research that suggests neurological effects from T. gondii may be responsible for up to 17% of auto accidents and 10% of suicide attempts. Studiesinvolving first-episode schizophrenia report that those who are positive for T. gondii exhibited more severe symptoms. Some researchers are investigating potential links to Parkinson’s and Alzheimer’s disease as well.