Puppetry of a Parasite: How Toxoplasma gondii Manipulates its Host

To a parasite, a host is more than just a home. They can be a source of food, protection from extreme conditions, or, in the case of Toxoplasma gondii, a vessel to get themselves from A to B. Unfortunately for the host, T. gondii not only hitches a ride but controls where they go. In this blog, we discuss new research from Meyer et al. (2022), suggesting that mild manipulation from T. gondii increases a gray wolf’s risk-taking behaviors, with potentially fatal consequences.

The Manipulation Hypothesis

A parasite like T. gondii is driven by the most basic instinct that all organisms share: survive and multiply to ensure the next generation of the species. Hosts are key to this survival; T. gondii utilizes multiple hosts during its lifecycle. Some, like gray wolves, are just intermediate hosts, acting as stepping-stones for the parasite to reach the final, definitive host.

The infection caused by T. gondii is called toxoplasmosis. All warm-blooded species are susceptible to toxoplasmosis, but only felids (types of cats) can be the definitive host. They are the only animals in which sexual reproduction can occur, leading to the production of oocytes that are released into the environment for ingestion by unsuspecting animals, spreading the disease. With a limited range of definitive hosts, how can T. gondii guarantee that they ever actually reach one? They can’t, but they have a few tricks to push the odds in their favor.

Healthy hosts generally remain asymptomatic, which keeps them alive and means the parasite can exist undetected. However, it’s becoming increasingly apparent through experimental research that chronic toxoplasmosis leads to the production of dopamine and testosterone, increasing aggression and risk-taking. This brings an intermediate host closer to a felid.

An early example came from Berdoy et al. (2000), who investigated how T. gondii influences rat predation by cats. Rats, like most prey animals, have evolved many anti-predatory behaviors. One of these is an aversion to the smell of their aggressors. The researchers compared the response of infected and uninfected rats to cat urine, finding that infected rats showed little avoidance of areas with urine, unlike their healthy counterparts. In a natural setting, this risk-taking with cats around would lead to higher rates of predation. Not great for the rats, but it works in T. gondii’s favor.

Responses like these are examples of the “manipulation hypothesis”, where parasites alter the behavior of their host for their own gain. In the case of T. gondii, that’s improved transmission rates to felids.

Yellowstone National Park

As important as experimental studies are, little research has investigated wild animals. The impact of toxoplasmosis on intermediate host behavior needs to be demonstrated in a natural setting. Meyer et al. (2022) sought to change this, identifying Yellowstone National Park (YNP) as an ideal study site. YNP is a biodiverse ecosystem, but two species of note are gray wolves and cougars. These act as intermediate and definitive hosts of T. gondii, respectively. Though the two carnivores generally select for different habitats, there are areas of overlap that could act as transmission zones for T. gondii.

The main aim of the study was to work out if/how T. gondii influences gray wolf risk-taking. To do this, the researchers first defined risk-taking with a few characteristic behaviors. These were:

1. Dispersing from a pack.
2. Becoming a pack leader.
3. Approaching people or vehicles.

Decades of data already existed on gray wolves at YNP due to previous work looking at predator-prey dynamics, population dynamics, behavior, and canine pathogens (Smith et al. 2020). Up to 20 wolves were captured and radio collared each year between 1995 and 2021, to track their future movements. Wolf packs were also directly observed for risk-taking behaviors up to 250 times a year over this period.

Serological screenings to detect antibodies against T. gondii in captured wolves revealed any infected individuals. By pairing the serological and behavioral data, T. gondii infections could be linked to risk-taking. Of course, lots of factors can influence behavior, so controls were put in place for variables such as sex and habitat types.

The results showed that territory overlaps between wolves and cougars made excellent predictors for toxoplasmosis. HCO (high cougar overlap) wolves were nearly nine times more likely to be infected than LCO (low cougar overlap) wolves. Infected wolves were also prone to exhibiting two of the three risk-taking behaviors. They were 11 times more likely to disperse from their pack and 46 times more likely to become a pack leader compared to seronegative individuals. Both behaviors are key to controlling wolf distributions and could lead a whole pack to an infectious area, not just the infected wolf. If a dispersing wolf survives, it will likely establish a breeding population in a new territory; a pack leader has a greater influence over group decisions, such as movements to new areas.

It appears that by increasing risk-taking, T. gondii increases the likelihood of a wolf entering cougar territory. This encourages infections to spread in two ways. The wolves may come into contact with infected cougars or their shed oocytes, and the cougars may consume infected wolves, completing T. gondii’s lifecycle.

Just like the experimental rats, wolves are puppets to their parasites. Only T. gondii comes out as a winner.

Conclusion

The value of research like this should not be understated. Since host behaviors are being influenced from the shadows, it would be easy to miss the cause. The impact of T. gondii extends far beyond its host though; control over one wolf can lead to community-level changes. Demonstrating this in a natural setting is pivotal for supporting previous works in the laboratory.

The implications of toxoplasmosis should be considered in a range of wildlife research. Who knows which animals are being subtly controlled? Even though carnivores like gray wolves are high up in the food chain, countless years of anti-predatory evolution can be undone by a simple parasite.