New research led by a team at the Karolinska Institutet in Sweden reveals for the first time what the common “cat litter parasite” Toxoplasma gondii does once it gets into the brain. The study is important in the light of recent observations linking the parasite to risk-taking and other human behaviours, and associations with mental illness.
The researchers write about their findings in a paper published online on 6 December in the journal PLoS Pathogens.
Infection by Toxoplasma gondii or Toxoplasma is called Toxoplasmosis. Estimates suggest between 30 and 50% of the global human population is infected. In Sweden the figure is nearer 20%. In the US, the Centers for Disease Control and Prevention (CDC), puts the number of infected men, women and children at 60 million. Animals can also become infected, especially domestic cats.
People usually contract the parasite by eating poorly cooked meat: according to the CDC, toxoplasmosis is the leading cause of death from foodborne illness in the US. Another way people become infected is by touching cat feces, hence the expression “cat litter parasite” because one way of touching cat feces is handling the cat litter tray.
The vast majority of people infected have few symptoms because their immune system usually stops the parasite from causing illness. In newly infected adults the parasite can cause mild flu-like symptoms, and then it usually enters a chronic dormant phase which was thought to be symptom free.
However, when the parasite enters the brain of fetuses, and people with weak immune systems, it can be fatal. Because of this risk, uninfected pregnant women should not touch cat litter trays.
There is an emerging view that the toxoplasmosis parasite is active to some extent during what was previously regarded as a purely “dormant phase”.
For example, rats infected with the parasite lose their fear of cats, and are even attracted by their scent, making them easy prey. Scientists have suggested this is how the parasite assures its own survival and propagation: the cats eat the infected rats, shed more parasite through their feces, and that in turn helps to infect more rats.
Other studies have found schizophrenia, depression, anxiety, and other mental diseases are more common in people with toxoplasmosis, and there is also evidence to suggest infection by the parasite is linked to more extroverted, aggressive and risk-taking behavior.
In a study published in the July 2012 issue of the Archives of Psychiatry, researchers from Denmark’s Statens Serum Institut and the University of Maryland in the US, found that women carrying IgG antibodies to Toxoplasma gondii when giving birth have a higher risk of self-harm or suicide later on.
While such a description sounds alarming, study senior author Antonio Barragan, researcher at the Center for Infectious Medicine at Karolinska Institutet and the Swedish Institute for Communicable Disease Control, says:
“At the same time, it’s important to emphasize that humans have lived with this parasite for many millennia, so today’s carriers of Toxoplasma need not be particularly worried.”
The researchers didn’t examine how the toxoplasmosis parasite changes host behavior, they were more interested in what it does in the brain.
They found that it takes over one of the brain’s neurotransmitters: the chemical messengers that carry signals between various parts of the brain.
In one test tube experiment, they infected human dendritic cells with the parasite. Dendritic cells form the frontline of the immune system, and play a key role in triggering and adapting immune responses. Once infected, the dendritic cells started secreting GABA, a chemical messenger.
In another experiment with live mice, the researchers tracked infected dendritic cells from their initial point of infection to other parts of the brain where they continued to affect the GABA system.
In their author summary, the researchers note:
“Dendritic cells are considered the gatekeepers of the immune system but can, paradoxically, also mediate dissemination of the parasite.”
“This study establishes that GABAergic signaling modulates the migratory properties of dendritic cells and that the intracellular pathogen Toxoplasma gondii sequesters the GABAergic signaling of dendritic cells to assure propagation,” they add.
GABA does a number of things, but one of them is to inhibit the sensations of fear and anxiety. People with mental illnesses such as schizophrenia, bipolar diseases, anxiety syndrome and depression show disturbances in GABA systems.
Barragan describes the parasite’s ability to make the immune cells secrete GABA as “very clever” and says the finding was “as surprising as it was unexpected”.
The researchers call for further studies.
“It would now be worth studying the links that exist between toxoplasmosis, the GABA systems and major public health threats,” Barragan suggests.
A grant from the Swedish Research Council helped fund the study.
Written by Catharine Paddock PhD