Tag: parasites

Persistent Parasites are Not Totally Protected from Immune Response

Source: Wikimedia CC0

Most humans have long-lived infections in various tissues, including in the nervous system, that typically do not result in disease. The microbes associated with these infections, such as Toxoplasma gondii, enter a latent stage during which they quietly hide in cells, playing the long game to evade capture and ensure their own survival. But a lack of natural models to study these quiescent stages has led to gaps in scientists’ understanding of how latency contributes to pathogen persistence and whether these stages can be targeted by the immune system.

Now, a team led by University of Pennsylvania School of Veterinary Medicine researchers shows that the immune system indeed recognises the latent stage of the parasite Toxoplasma gondii, which causes toxoplasmosis. The work, published in Nature Microbiology, challenges some common assumptions about how the immune system deals with infections in the brain. Senior author Christopher A. Hunter, professor at PennU Vet, says this knowledge supports the idea that Toxoplasma gondii cysts can be targeted and perhaps even cleared, and the findings have implications for other infections and potential future therapies. The paper also demonstrates how cysts promote the mutual survival of the parasite and host.

In its latent stage, Toxoplasma gondii forms long-lived cysts in neurons in the brain, which helps the parasite evade the host’s immune response. In this study, the researchers found that certain T cells can target neurons containing cysts, thereby promoting parasite control. But there’s a tradeoff: They also found that when cysts are not formed, there is an even higher parasite burden and increased damage to the brain. The study is published in Nature Microbiology.

“There’s this balance of the pathogen needing to take hold in the host but not expand so much that it’s detrimental to the host, because if the host dies, the pathogen may not survive,” says author Lindsey A. Shallberg, who at the time of the research was a doctoral student in Hunter’s lab.

Toxoplasma gondii causes toxoplasmosis, an infection that is asymptomatic for most healthy people but poses a greater risk for those who are immunocompromised or pregnant. It is caused by eating contaminated, poorly cooked meat and by exposure to infected cat faeces, as felines are the only animal in which the parasite can sexually reproduce.

Co-author Julia N. Eberhard, an immunology doctoral student, points to two findings that run counter to preexisting literature and common notions among immunologists. She says scientists long thought that Toxoplasma gondii cysts could hide out in neurons to prevent immune recognition, but this study showed that “neurons aren’t this complete refuge for pathogens.”

This image shows Toxoplasma gondii (red) and a neuron (green) in a mouse brain.
(Image: Courtesy of Anita Koshy)

Eberhard says another commonly held belief was that the parasite needs to form cysts to be able to persist, but in looking at a parasite strain that couldn’t convert to the cyst stage, the researchers found that the immune system did not clear the parasite. They could still identify parasites in mice six months later, which Eberhard found very surprising.

Mathematical modelling independently confirmed experimental findings and indicated that immune pressure on the latent stage of Toxoplasma gondii could explain the observed rise and fall in cyst numbers. This was done by Aaron Winn, a doctoral student in the Department of Physics and Astronomy.

Shallberg says this paper came about because co-author Sebastian Lourido, an associate professor of biology at MIT, had identified the key molecular mechanism that allows the parasite to become latent and wanted to know what would happen if the parasite could not form cysts. In addition, co-author Anita Koshy, a neurologist and scientist at the University of Arizona, had evidence that some neurons could rid themselves of this infection. 

While Toxoplasma gondii is a relevant microorganism to study in and of itself, it is also useful in furthering scientists’ understanding of nervous system infections with latent stages in humans that don’t have mouse models, such as cytomegalovirus. “What makes it special is the fact that it’s a tractable model that we can use in the lab and then apply what we’ve learned to other infections,” Shallberg says.

Looking ahead, Hunter says that his laboratory continues to investigate whether T cells directly recognise the neurons and to study the T cell response in more detail.

Source: University of Pennsylvania

Ticks’ Trick: Using Static Electricity as a Grappling Hook

Photo by Pixabay

Ticks can be attracted across air gaps several times larger than themselves by the naturally accumulated static electricity of their hosts, researchers at the University of Bristol have discovered. This makes it much easier to finding hosts to parasitise because ticks cannot jumping, making this is the only mechanism by which they would be able to latch onto hosts that are beyond the reach of their tiny legs.

The findings, published today in Current Biology, are the first known example of static electricity being implicated in the attachment of an animal to another animal.

Lead author Sam England from Bristol’s School of Biological Sciences explained: “We knew that many animals, including humans, can accumulate quite significant electrostatic charges.

“We see this when we get a static shock after bouncing on a trampoline, or when rubbing a balloon on our hair, for example. But this electrostatic charging also happens to animals in nature when they rub against objects in their environment like grass, sand, or other animals. These charges are surprisingly high, and can be equivalent to hundreds if not thousands of volts — more than you get out of your plug sockets at home! Importantly, static charges exert forces on other static charges, either attractive or repulsive depending whether they are positive or negative.

“We wondered whether the static charges that mammals, birds, and reptiles naturally accumulate could be high enough that parasitic ticks could be lifted through the air by electrostatic attraction onto these animals, therefore improving their efficiency at finding hosts to feed on.”

The team initially tested the idea by bringing statically charged rabbit fur and other materials close to ticks and observing whether they were attracted to them.

They witnessed the ticks being readily pulled through the air across air gaps of several millimetres or centimetres (the equivalent of humans jumping up several flights of stairs) by these charged surfaces, and so investigated further.

Sam continued: “First, we used previous measurements of the typical charge carried by animals to mathematically predict the strength of the electric field that is generated between a charged animal and the grass that ticks like to sit on and wait for hosts to pass by.

“Then, we placed ticks underneath an electrode, with an air gap in between, and increased the charge on the electrode until the ticks were attracted onto the electrode. By doing this we were able to determine the minimum electric field strength at which the ticks could be attracted. This minimum electric field was within the order of magnitude predicted by the mathematical calculations of the electric field between a charged animal and grass, therefore it is likely that ticks in nature are attracted onto their hosts by static electricity.”

There are several wider implications and potential applications to these findings. Firstly, the phenomenon likely applies to many other parasitic species that want to make contact and attach to their hosts, such as mites, fleas, or lice, and so it could be a universal mechanism for animals to make contact with and attach onto each other.

Beyond the purely scientific implications, the discovery opens the door for new technologies to be developed to minimise tick bites in humans, pets, and farm animals, such as developing anti-static sprays.

Sam concluded: “We have now discovered that ticks can be lifted across air gaps several times larger than themselves by the static electricity that other animals naturally build up. This makes it easier for them to find and attach onto animals that they want to latch onto and feed from. Until now, we had no idea that an animal could benefit from static electricity in this way, and it really opens up one’s imagination as to how many invisible forces like this could be helping animals and plants live their lives.”

Now the team plan to investigate whether the ticks are capable of sensing the approaching electrostatic charge of their prospective hosts.

Source: University of Bristol