Scientists have discovered how Toxoplasma, one of the most common parasites in humans, hacks the immune cells of its hosts so that it can ride them around the body with alarming speed, reports a new study. The research reveals new secrets about this pernicious parasite, which reproduces in cat hosts and has infected at least one third of the global population, and sheds light on how other infectious diseases spread in humans and animals.
Toxoplasma is widespread in warm-blooded animals and can be dangerous in some cases—especially for pregnant women and fetuses—though most people who carry the pathogen do not develop any harmful symptoms. The parasite is a public health concern as well as a scientific curiosity due to some of its ghoulish behaviors. For example, Toxoplasma relies on cats as hosts for its reproductive cycle, so it has evolved a devious way to get into the brains of rodents to make them less alert to predators, upping the odds that they will be eaten by cats and thereby allowing the parasites to breed. It’s for this reason that Toxoplasma is often said to turn its rodent hosts into “zombies.”
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Now, scientists led by Arne ten Hoeve and Antonio Barragan, molecular bioscientists at Stockholm University, have identified a key mechanism that distinguishes Toxoplasma as such an effective parasite in humans. By examining the parasite in cell cultures, the team discovered that it “hijacks” immune cells by injecting them with a protein called GRA28 that makes the cells forget their identity, according to a study published on Friday in Cell Host & Microbe.
“Toxoplasma infects so many animal species, including humans,” Barragan said in an email to Motherboard. “The parasite so efficiently spreads in the infected host, reaching sites that normally are inaccessible to most microbes, such as the developing fetus or the brain.”
While Toxoplasma’s behavior-modifying effects in rodents are well-known, its effects in humans are still debated. The literature shows devastating effects in the brains of people who are immunocompromised in the form of encephalitis, and some research has been done on the potential behavioral effects but remains inconclusive.
“The fact that Toxoplasma manipulates immune cells has been known for a while, however exactly HOW has remained enigmatic,” he continued. “Toxoplasma does this manipulation in a very clever way: by invading immune cells, injecting proteins and this way taking over control of the immune cells that PARADOXICALLY are there to kill the parasite. After invasion, the immune cell functions instead as a shuttle for the parasite, like a Trojan horse. This tells us that Toxoplasma probably understands our immune system better than we humans do.”
Previous studies have pinpointed GRA28 as an important tool that the parasite uses to take over macrophages, which are immune cells that remain stationary in bodily tissues. Barragan and his colleagues employed advanced microscopic imaging techniques to peer into the molecular processes at work during these interactions.
The results suggest that the parasite uses GRA28 to sneak into the nucleus of macrophages so that it can repress and activate the cell’s gene expressions. In this way, GRA28 essentially makes macrophages forget that they are motionless parts of the immune system, and convinces them that they are, instead, dendritic cells, which are highly mobile immune cells. It’s almost as if the parasites are able to hotwire the immune cells into tiny fast-moving vehicles that allow them to spread rapidly through the body.
“The findings teach us a lot,” Barragan said. “First, the results are humbling: they teach us how little we know in fact about diseases and that microbes can teach us if we only have the patience to study their biology. This is nothing solved in one or two tweets, rather years of hard work by many and in international cooperation among researchers from US and France.”
“Then, in the next phase this knowledge on how disease is caused can be applied to cure and prevention,” he concluded. “We hope this knowledge will serve not only to understand Toxoplasma infections, but also how other infections (such as viruses and bacteria) spread in the body and make us sick.”
