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We finally know how the 'mind-altering' cat parasite controls our immune response

1 in 2 people are infected.

BEC CREW
28 NOV 2016
 

Up to 50 percent of global population is infected by the 'cat parasite' Toxoplasma gondii, and in some areas, the infection rate is as high as 95 percent. Unless you get tested, there’s no way of knowing that you’re infected, but it’s been associated with a number of mental disorders, such as schizophrenia and bipolar disorder.

Yep, Toxoplasma is everywhere, and while the jury is still out on how much it actually messes with our minds, scientists have finally figured out why it’s so good at dodging our body's immune response.

 

For the uninitiated, Toxoplasma is a cat-borne parasite that causes Toxoplasmosis - a disease that is considered 'asymptomatic' in most healthy people, but can lead to a range of other disorders in those with compromised immune systems, such as pregnant women and the elderly.

While most doctors wouldn’t recommend you bother testing for Toxoplasma unless you’re at risk of getting sick from it, studies have turned up curious links between it and certain host behaviours.

At the forefront of this research is Jaroslav Flegr, an evolutionary biologist at Charles University in the Czech Republic, who once asserted that, "Toxoplasma might even kill as many people as malaria, or at least a million people a year,” because of how it appears to change our response to dangerous situations.

Past research has found that when mice are infected by Toxoplasma, they lose their innate fear of cat urine, and display signs of impaired working memory. 

It's been hypothesised that the parasite messes with rodent brains to help it complete its life cycle, and for years now, scientists have been investigating if something similar is occurring in its human hosts. 

"There is a fascinating association between Toxoplasma infection and psychiatric diseases including schizophrenia and bipolar disorder," says parasite researcher Chris Tonkin from the Walter and Eliza Hall Institute in Australia.

 

While there appears to be something strange going on with people infected by Toxoplasma, the scientific evidence is frustratingly inconclusive

But there’s one thing about Toxoplasma that’s far from ambiguous - its ability to manipulate our immune response. 

The fact that in some areas of the world, almost the entire local population is infected shows just how successful this parasite is, and its success lies in its ability to strike a delicate balance with our immune system.

Toxoplasma has managed to keep the body's immune response to it low enough to ensure that it can still thrive in its human hosts, but high enough that those who are infected can live a healthy life as one giant parasite incubator.

And now scientists have figured out how.  

"The parasite rewires the host's inflammatory response," says Matthew Bowler from the European Molecular Biology Laboratory. "It completely subverts the chain reaction that would normally trigger our body's defences."

Under normal circumstances, when cells in your body detect a parasite, a series of molecular signals will activate a protein called p38α, prompting it to move into the cells' nuclei. Here, it activates the genes that trigger an inflammatory response to eliminate the pathogen.

Interestingly, rather than simply blocking those signals, Toxoplasma gets its way by doing the exact opposite: Bowler and his team found that the parasite actually kickstarts the human inflammatory response, and proceeds to manipulate it according to its own needs. 

The research was based on a previous study led by Mohamed-Ali Hakimi from the Institute of Advances Bioscience in France, who found that Toxoplasma secretes a protein called GRA24 that activates the protein p38α directly, before the body's own immune system can get involved.

The team has now figured out that GRA24 binds much more strongly to p33α than the cell's own proteins do, and this allows it to control the level of immune response that the body dishes up.

At the same time, the Toxoplasma protein also prevents the body from switching off the inflammatory response, which is why the disease can be so dangerous in people who already have weakened immune systems.

"The tight control of the inflammatory signalling prevents either too weak a response leading to host death, or too strong a response preventing invasion," the team concludes.

While it's a little disconcerting to find out just how easily this parasite can manipulate our entire immune system, the research could help scientists to develop more effective anti-inflammatory drugs.

Right now, they're all focussed on blocking the activity of p33α, but Toxoplasma has demonstrated how a similar effect could be derived from finding an alternative way to activate and control it.

Classic cats. We feed them and love them and all we get in return is a parasite that knows more about our immune response than we do. 

The research has been published in Structure.

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