A food-borne parasite that infects domestic cats can get inside the human brain by commandeering special cells of the immune system which it uses as a Trojan horse to enter the central nervous system, a study has found. Scientists believe they have finally discovered the mechanism that allows Toxoplasma gondii a single-celled parasite to pass from the human gut to the brain where it may cause behavioural changes.
Researchers have shown that the parasite can infect the dendritic white blood cells of the immune system causing them to secrete a chemical neurotransmitter that allows the infected cells, and the parasite, to cross the natural barrier protecting the brain. Toxoplasma gondii can live in many different species but it can only complete its life cycle in cats, which secrete the parasite in their faeces.
Studies have shown that toxoplasma affects the behaviour of rats and mice, making them more likely to be eaten by cats, thereby completing parasite's complex life-cycle. Latest figures released in September by the Food Standards Agency(UK) show about 1,000 people a day in Britain 350,000 a year are being infected with toxoplasma, probably from either direct contact with cats or by eating poorly-cooked meat or vegetables.
Up to 40 per cent of the British population are believed to be infected with toxoplasma and although the vast majority show no apparent symptoms, there is a risk to unborn children if their mothers become infected for the first time during pregnancy. However, recent studies have also suggested that toxoplasma may be a trigger for psychological disturbances in humans, including schizophrenia, although the research has fallen well short of showing a cause-and-effect.
Antonio Barragan of Sweden's Centre for Infectious Diseases at the Karolinksa Institute in Stockholm said that when infected with toxoplasma human dendritic cells, which are not part of the central nervous system, begin to secrete a neurotransmitter called GABA which is normally produced by brain cells.
"For toxoplasma to make cells in the immune defence to secrete GABA was as surprising as it was unexpected. This was unknown. It means that the parasite had the capacity potentially to manipulate the central nervous system," Dr Barragan said. The study, published in the on-line journal Plos Pathogens, used human dendritic cells growing in a test tube, but it also showed that infected dendritic cells pass more easily than uninfected cells into the brains of laboratory mice.
"We've shown that it happens in human dendritic cells taken from healthy donors and also proved that the same thing happens in the mouse model. It shows that the parasite is using dendritic cells as a sort of Trojan horse to transport itself from the human gut to the brain," Dr Barragan said.
"We've not looked at behaviour changes in people infected with toxoplasma, as that's been dealt with by previous studies. Instead, we've shown for the first time how the parasite behaves in the body of its host, by which I mean how it enters the brain and manipulates the host by taking over the brain's neurotransmitters," he said.
GABA, or gamma aminobutyric acid, is involved, among other things, in inhibiting the sense of fear and anxiety. Rats and mice infected with toxoplasma show little fear of cats and Dr Barragan suggested that infected dendritic cells may continue to stimulate the production of GABA once the cells have entered the brain.
However, other scientists have shown that toxoplasma is capable of producing another nerve substance called L-dopa which is a chemical precursor to the dopamine neurotransmitter, which may be another route to altering mammalian behaviour.
"Many neuropsychiatric disorders implicate a dysregulation of several neurotransmitters. If one is affected, this may affect the others, or the balance between neurotransmitters. How GABA specifically acts in the equation is a question for the future," Dr Barragan said.
Scientists emphasised that the jury is still out on whether toxoplasma is capable of influencing the behaviour or mental state of infected people given the preliminary nature of the studies showing a tentative link between the parasite and human behaviour. "We believe that this knowledge may be important for the further understanding of complex interactions in some major public health issues that modern science still hasn't been able to explain fully," Dr Barragan said.
"At the same time, it's important to emphasise that humans have lived with this parasite for many millennia," he said.