A quarter of people carry this cunning critter (Image: BSIP VEM/SPL)

The Toxoplasma parasite is an unusually devious operator. When it infects mice, it alters their behaviour so they become fearless enough to seek out cats and get eaten. But exactly how it did this was a mystery.

Now it appears that the parasite hijacks its victim’s immune system, causing it to produce a chemical normally found in the brain. The discovery suggests that the brain and immune system might have evolved using similar processes to control their behaviour, including electrical and chemical signals now known mainly in nerves.

Toxoplasma gondii spends part of its life in a cat’s gut, then spreads to mice via cat droppings. It invades their brains and causes them to behave fearlessly towards cats – quickly returning the parasite to a cat’s gut and completing its life cycle.


The parasite can use other animals as a host, and can spread to humans via infected, uncooked meat as well as cat droppings. Acute infection can harm a fetus, so pregnant women are told to avoid cat litter boxes. A quarter of people have a lifelong Toxoplasma infection and may suffer psychological effects, including increased recklessness.

Antonio Barragan of the Karolinska Institute in Stockholm, Sweden, has now discovered that the parasite’s mind-bending abilities could be a side effect of the way it hijacks the immune system. Invaders like Toxoplasma normally get engulfed by white blood cells called dendritic cells (DCs), a process that helps other immune cells learn to recognise them.

Cell hijack

Toxoplasma, however, hijacks DCs. It not only lives and multiplies inside them, it makes them “hypermobile”, crawling more actively through tissue and migrating faster around the body than usual. “The DCs are vehicles that transport the parasite around the body,” says Barragan.

Barragan’s team has found that the parasite does this by turning on a set of genes within DCs for producing and secreting a chemical called GABA. This was a surprise as GABA is a neurotransmitter, carrying signals in the brain from one nerve cell to another. The researchers found that DCs, like a few other non-neural cells, carry receptors for GABA.

The GABA that DCs make stimulates their own receptors, causing the voltage across the cell membrane to change, just as it would in a nerve cell membrane. This somehow makes the DCs more mobile and able to spread the parasite: drugs that block GABA stopped the cells becoming hypermobile and this led to fewer parasites in the brain.

The fact that immune cells respond to a neurotransmitter raises the possibility that mechanisms thought to be unique in nerves may also operate in many other types of cell.

Intriguingly, says Barragan, as a neurotransmitter in the brain, GABA reduces fear and anxiety. A brain invaded by parasite-infested DCs churning out GABA may well become inappropriately fearless. Alternatively, the parasite might be able to invade brain cells too and turn on their GABA genes.

“It’s hard to say which came first,” says Barragan, the parasite’s ability to hijack the brain, or the immune system. Either way, it is GABA that gets the parasite where it wants to go: down a cat’s throat.

Journal reference: PLoS Pathogens, doi.org/jxk