Toxoplasma gondii: Curiosity killed...the mice

A new study finds that the toxoplasmosis parasite settles cysts in the brains of "intermediate hosts", affects their behavior and making them more exposed to cats, the definitive parasitic host.

Infected mice develop curiosity towards their predators, ensuring the parasite transmission process

A new study finds that the toxoplasmosis parasite settles cysts in the brains of "intermediate hosts", affects their behavior and making them more exposed to cats, the definitive parasitic host.

The toxoplasma gondii is a parasite that can be passed on to humans through exposure to undercooked meat, poorly washed fruits and vegetables, or contact with an infected cat's excrement. Toxoplasmosis establishes a persistent chronic infection in the form of cysts located in the muscles and the brain, where it remains "dormant".

Humans, however, remain an accidental host for the parasite, and the infection remains latent unless immunosuppressed or untreated, in which case it can lead to death. The infection also predisposes to certain neurological diseases, such as schizophrenia, Parkinson's or Alzheimer's disease. Toxoplasmosis is also dangerous for the fetus if the mother has a primary infection during pregnancy. The baby's brain, which is not protected by the mother's immune system, can become infected, causing neurological damage and even triggering an abortion.

Destination: Cat

The ultimate target of toxoplasma, that is, its "definitive host", is the cat. More precisely, the cat's intestines. It is there where the parasite can reproduce by making oocytes (which are particularly infectious and are then expelled via excrement). To achieve this, the parasite first uses an "intermediate host", namely birds and mice. The intermediary host, in order to close the cycle of transmission, needs to be eaten,  and even more, purposely exposing itself to be eaten. Toxoplasma is therefore capable of altering their behavior, transforming, for example, the mice's fear of cats into an attraction towards them.

Researchers at the University of Geneva (UNIGE) have shown that as a matter of fact, a variety of behaviors of these intermediate hosts are modified: for example, anxiety, stress, and curiosity. The more the parasite is present in the form of cysts in the brain, the more the mouse is uninhibited. "We wondered how the toxoplasma manages to set up such a specific mechanism, namely the exclusive alteration of a mouse's fear of cats," explains Madlaina Boillat, a researcher at the Department of Genetics and Evolution of UNIGE's Faculty of Science.

General disinhibition observed

To determine whether the change in mice's behavior was solely related to their response to felines, the researchers first tested infected rodents’ general anxiety by observing their sense of security and curiosity and then comparing it with those of healthy mice. "We immediately noticed an attitude difference in infected mice, which were more curious and less stressed," noted Ivan Rodriguez, also a professor at the Department of Genetics.

The researchers then placed sick and healthy mice in the presence of lynx urine. "Unlike the healthy mice, the mice infected with the parasite were all attracted by the smell, which normally makes them flee," adds Madlaina Boillat. They then extended the experiment to other predators of the mice, such as rats. "We placed a sleeping rat in the cage of the healthy mice, which immediately showed a panic reaction. On the contrary, the infected mice even wandered over the rat," remarks Ivan Rodriguez.

These experiments show that, contrary to previous knowledge, it is not only the fear of the cat that is inhibited in the infected mice, but their entire behavior is altered. It remains to be understood how the parasite performs this feat.

What is certain is that behavioral impairment is related to the number of cysts. "Using the technique of light-sheet microscopy, we were able to observe the brain with an extremely high resolution and found that the whole brain was invaded by cysts, particularly the cortex; while the hypotheses leaned towards the amygdala, which is involved in the innate response of fear," said Dominique Soldati-Favre, professor in the Department of Microbiology and Molecular Medicine. "The change in behavior is perceptible as early as with the presence of 200 cysts in mice, with a real effect on fear within a range of between 500 and 1000 cysts," she explained. The researchers added that by comparison, the behavior of infected humans also seems to be slightly modified according to the degree of inflammation of the brain.