Parasite hijacks the mind of its host

t_gondii_cyst_brain.jpgIt sounds like something from a science fiction film: a parasite that enters the brain and manipulates the behaviour of its host. But this is not science fiction – it’s very real. The parasite is a unicellular organism called Toxoplasma gondii, which “hijack[s] the mind” of its host, according to Ajai Vyas, lead author of a paper, published online last week in the Proceedings of the National Academy of Sciences, describing the effects of T. gondii infection on the behaviour of rodents.

T. gondii is but one of thousands of different types of manipulative parasites, all of which alter the behaviour of their hosts to increase the efficiency with which they are transmitted. Like the malarial parasite Plasmodium falciparum, to which it is closely related, T. gondii is a protozoan. It has a complex life cycle involving transmission between, and infection of, at least two species. The reproductive phase of the life cycle takes place in the cells lining the intestine of the cat, which is the primary host. Here, T. gondii forms structures called oocysts, which consist of fertilized eggs enclosed in a thick wall. These serve to transfer the parasite to its other host, a rodent. The oocysts are extremely resilient – they can survive treatment with disinfectants such as bleach, and exposure to temperatures as low as -12°C. After being excreted in cats’ faeces, they can survive in soil for up to a year, until ingested by rodents.

Normally, rodents have a aversion to the smell of a pheromone found in cat urine, for obvious reasons. This aversion is innate – rodents fear the smell of cats’ urine even if they have never encountered it before, so this fear seems to be hard-wired. In 2000, researchers from the University of Oxford discovered that T. gondii manipulates this fear behaviour – infected rodents are mildly attracted to, rather than averse to, the smell of cat urine. This is a case of fatal attraction – of course, attraction to the smell of cats’ urine makes infected rats and mice more susceptible to predation, thus increasing the probability that the parasite will complete its life cycle.

Vyas and his colleagues presented infected and uninfected rodents with a series of choose tests. The animals were placed in an enclosed circular area that had been divided into four sections. One of the sections was laced with bobcat urine, another with rabbit urine. The amount of time spent by each group of animals in each section of the area was then measured. Sure enough, in confirmation of the earlier findings, it was found that infected animals spent far more time than uninfected ones in the section laced with bobcat urine. T. gondii infection had effectively abolished their aversion to the odour of the urine, and made them mildly attracted to it instead.

The animals were then trained to fear a region of their enclosure. On several occasions, they were placed in the middle of the arena, where electric shocks were administered to their feet. When this was repeated a number of times, the association of the middle of the arena and electric shocks was strengthened, and the animals displayed fear behaviour – standing still – when placed in that part of the enclosure (i. e. the animals had been classically conditioned to fear that part of the arena). When tested later, both infected and uninfected animals froze when placed in the centre of the arena, because they expected to receive a shock to their feet. Infected animals also remained fearful of the odour of foods they had not encountered before, and still became anxious when placed in an open space. Infected rodents continued to exhibit other anxieties and are still capable of learning to fear other stimuli. Thus, rather than altering the host’s sense of smell, or having a generalized effect on fear behaviour, T. gondii specifically targets and modifies the response of rodents to the smell of cat urine.

Vyas’s group labelled the parasites they used in their study with a bioluminescent molecule called luciferase, enabling them to visualize how it spreads through the body during the course of infection. This showed that it initially infects peripheral tissues before making its way to the brain. 1 month after infection, T. gondii was no longer detected in peripheral tissues, but was found solely in the brain. Dissection of the rodent’s brains showed that the parasite had formed cysts in a variety of brain regions, including the olfactory bulb hippocampus, prefrontal cortex, all of which have previously been shown to be responsive to cat odour, as well as several other regions that are unresponsive to cat odour. But the greatest densities of cysts were found in the amygdala, a region of the limbic system involved in the encoding of fearful memories. (The image at the top shows a cyst formed by T. gondii in brain tissue.)

So, T. gondii not only targets the neural circuitry involved in fear, but it also alters a specific response mediated by that circuitry. Exactly how remains unclear, but it is likely that the parasite synthesizes chemicals that mimic the rodents’ own neurotransmitters. These chemicals apparently manipulate the rodent’s response to cat urine by perturbing the neurochemistry of the amygdala and connected structures. Specifically, the authors speculate that T. gondii has an effect on neuromodulation mediated by the transmitters dopamine and noradrenaline.

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But the plot thickens, and takes a somewhat sinister turn. T. gondii can infect most species of warm-blooded animals, including humans, who may become infected by coming into contact with cat faeces or by eating undercooked meat. It is estimated that some 40% of the world’s people harbour the parasite, and that up to 80% have been infected at some time in their life. In people with a compromised immune system, such as AIDS patients and pregnant women, toxoplasmosis, the disease caused by T. gondii infection, can, in some cases, be fatal (this is why pregnant women are told to stay away from cat litter). But in the vast majority of people, T. gondii infection results is asymptomatic.

Or so it would seem…

A number of recent studies have suggested that T. gondii can cause subtle changes in the personalities and behaviour of infected people. Last year, for example, Jeroslav Flegr, a parasitologist at Charles University in Prague, found that women infected with the protozoan are more likely to give birth to boys than to girls. Thus, by influencing the boy-to-girl birth ratio, T. gondii may have a considerable effect on the human population. Flegr also administered a battery of psychological tests to infected and uninfected people, and compared the results. His preliminary data suggest that T. gondii can alter the behaviour of humans as well as that of rodents. Nicky Boulter, a research fellow at the Institute for Biotechnology of Infectious Diseases, at the University of Technology in Sydney, Australia, summarizes the findings:

Infected men have lower IQs, achieve a lower level of education and have shorter attention spans. They are also more likely to break rules and take risks, be more independent, more anti-social, suspicious, jealous and morose, and are deemed less attractive to women. On the other hand, infected women tend to be more outgoing, friendly, more promiscuous, and are considered more attractive to men compared with non-infected controls. In short, it can make men behave like alley cats and women behave like sex kittens.

Epidemiological studies have also implicated T. gondii in some cases of schizophrenia. This is particularly interesting, especially when we consider the speculations of Vyas’s group about how the parasite manipulates neural circuitry in the amygdala. Because both dopamine and noradrenaline have also been implicated in schizophrenia, it seems plausible that any link between T. gondii and schizophrenia would likely be linked to the organism’s ability to alter the levels or activity of these neurotransmitters. Finally, Kenneth Lafferty, a biologist with the U. S. Geological Survey, has also found a positive correlation between of T. gondii infection and levels of neuroticism. But he goes so far as to suggest that the aggregate (or cumulative) effects of T. gondii infection in millions of people may have a major effect on collective personality, and could, therefore, subtlly influence human societies and cultures.

For more about Toxoplasma gondii, read this post by Carl Zimmer, and follow the links in it.

References:

Vyas, A., et al. (2007). Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. PNAS doi: 10.1073/pnas.0608310104. [Abstract]

Lafferty, K. D. (2006). Can the common brain parasite, Toxoplasma gondii, influence human culture? Proc R. Soc. B. 273: 2749-2755. [Full text]

Torrey, E. F. & Yolke, R. H. (2003). Toxoplasma gondii and Schizophrenia. Emerg. Infect. Dis. 9: 1375-1380 [Full text]

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Parasite manipulates host’s sense of smell

Parasites employ various strategies to increase their chances of reproducing. Some do so by manipulating the behaviour of their hosts. For example, when ready to sporulate, fungi of the genus Cordyceps synthesize chemicals which induce their ant hosts to climb the nearest plant, so that the area over which the fungal spores are distributed is maximized; similarly, gordian worms synthesize neuropeptides which mimic those produced by the host (a terrestrial insect), and which interfere with the host’s geotactic senses, causing it to jump into water so that the aquatic adult worm can emerge; and the platyhelminth worm Leuchchloridium macrosto- mum infects snails, turning their eye stalks into colourful blinkers, which makes the host more conspicuous to the molluscs which prey on them, and which are hosts for the remaining part of the parasites’ life cycle.

Acanthocephala is a phylum containing approximately 1,150 species of manipulative parasitic worm. The word Acanthocephala comes from the Greek roots Acantha, meaning ‘thorn’, and Kephale, meaning ‘head’; acanthocephalan worms, commonly known as spiny-headed or thorny-headed worms, are so named because one of their characteristic features is a retractable proboscis covered with tiny hooks. Acanthocephalans have a highly complex life cycle, involving the infection of one or more intermediate hosts. The intermediate hosts are always arthropods, and are usually the preferred food of the predator which acts as the worm’s definitive, or final, host.

Upon infection, the juvenile worm takes residence within the host’s body cavities. Because it lacks a digestive tract, the worm uses its proboscis to attach itself to the host’s intestinal wall, from which it absorbs nutrients. But acanthocephalans can only reach sexual maturity in the final host. The worms therefore manipulate the behaviour and physiology of their intermediate hosts, making them more conspicuous to the predatory fish; this increases the probability that the worms will complete their life cycle. The definitive host is always a vertebrate – a mammal, amphibian or bird; of the latter, ducks, geese and swans are common.

The intermediate hosts of the Pomphorhynchus laevis species are small (approx. 1 cm-long) freshwater crustaceans called amphi- pods. Previous studies have shown that amphipods infected with P. laevis are more susceptible to predation. Normally, amphipods remain in the dark areas to avoid capture by predators. This behaviour is mediated by a photophobic response, which causes the amphipods to be repulsed by light. But a P. laevis infection abolishes this photophobic response, and the amphipod’s response to light changes dramatically as a result. Rather than swimming away from a light source, infected shrimp move towards it. By swimming into open waters, they are much more visible to their predators. P. laevis infection also leads to increased production of haemocyanin, the invertebrate equivalent of haemoglobin, which carries oxygen around the body. The increased haemocyanin concentration produces a colour change, which further increases the conspicuousness of the infected shrimp, and facilitates the transmission of the parasite to the predatory fish, its definitive host.

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An amphipod (left) and the retractable proboscis of Pomphorhynchus laevis (right).

Sebastian Baldauf and his colleagues at the University of Bonn’s Animal Ecology Research Group have now discovered another trick that P. laevis carries up its sleeve. They have found that the worm manipulates the sense of smell of its intermediate host, the amphipod. As a result, the infected shrimp is attracted to the odour of fish that prey on it.

From a brook near their laboratory in Lucerne, Switzerland, Baldauf and his colleagues collected several hundred amphipods of the Gammarus pulex species (also known as the freshwater shrimp, or river shrimp), and 10 perch fish, which are known to prey on amphipods. Compartmentalized tanks containing separate sections were used to subject the amphipods to a series of choice tests. In each trial, an amphipod was placed in the middle of the lower section, which ran the entire length of the tank. After 5 minutes, a transparent net was placed 3 cm from the bottom of the tank, and a transparent divider was placed on top of the net, to divide the top section into two compartments of equal size. A perch was then placed in one of the two upper compartments, and the preference of the amphipod to one side of the tank or the other was observed.

In one experiment, the transparent net was glued to a transparent divider, so that only visual cues were available to the amphipods. In this set up, neither infected nor uninfected amphipods showed any preference for which side of the tank they stayed in. In another set up, uninfected amphipods were separated from the fish by jsut the transparent net, so that chemical signals could diffuse between the upper and lower sections of the tank. In this trial, the amphipods preferred the side without fish, and tried to escape from the fish by moving into the opposite side of the tank. When this trial was repeated with infected amphipods, it was found that they actually preferred the side of the tank containing the fish, and moved towards it.

The researchers could not determine the nature odour detected by the amphipods. The escape behaviour of uninfected shrimp, and the approach behaviour of infected shrimp, may be elicited by the odour of the predatory fish, or, possibly, by the odour of decom- posing products of shrimp already eaten by the fish. Nevertheless, the trials provide evidence that chemical cues are important for the recognition of predators by amphipods, and that P. laevis manipulates the amphipod olfactory system, such that infected shrimp are attracted to, rather than repulsed by, the odour of its predators. How it does so is, however, unclear. The researchers believe this to be the first example of a parasite manipulating its host’s olfactory system. The findings have been published in the International Journal of Parasitology.

References:

Baldauf, S., et al. (2007). Infection with acanthocephalan manipulates an amphipod’s reaction to a fish predator’s odours. Int. J. Parasit. 37: 61-65.

Bakker, T. C. M., et al. (1997). Parasite-induced changes in behavior and color make Gammarex pulex more prone to fish predation. Ecology 78: 1098-1104.

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