Plasmodium and Leishmania are fussy about where they live, able to survive only in certain types of cells. Most parasitic protozoa are equally choosy, but there are a few that can invade just about anything. One such species is Toxoplasma gondii, a creature that lives in undeserved obscurity. Few people know about Toxoplasma, even though there’s a fair chance that they are carrying it by the thousands in their brains. A third of all the people in the world are infected by it; in parts of Europe almost everyone is a host.
Although billions of humans carry Toxoplasma, we are not actually the parasite’s natural host. Normally it cycles between cats, domestic and wild, and the animals they eat. The cat releases Toxoplasma’s egg-like oocysts in its feces, and the oocysts can wait in the ground for many years to be picked up by an animal such as a bird, a rat, or a gazelle. In their new host, the oocysts hatch and the protozoa move through the body and look for a cell to make their home.
Toxoplasma is a close relative of Plasmodium, the protozoan that causes malaria, and it also is equipped with the same special machinery around its tip that blasts its way into a cell. But while Plasmodium can live only in liver cells and then red blood cells, Toxoplasma doesn’t much care. It muscles its way into just about any type of cell.
Once Toxoplasma has invaded a cell, it starts feeding and reproducing. After it has divided into 128 new copies, it tears the cell open, and the new parasites spill out, ready to invade fresh cells. After a few days, the parasite shifts gears. Now, instead of invading cells, it builds shells, each of which hides a few hundred Toxoplasma individuals. Every now and then, one of the cysts will break open and the parasites inside will invade cells and produce new Toxoplasma. But their descendants promptly build cysts of their own and vanish into them. There they will sit for years, until their host is eaten by a cat. Once inside their final host, they wake up again. They start dividing. Male and female sexual forms are born. They mate and make oocysts, and the cycle starts over again.
If a person should swallow Toxoplasma eggs, either in a speck of soil or in the meat of an infected animal, the parasite will go through this same fast-then-slow progression. Humans hardly know what’s happening during a Toxoplasma invasion; at worst it feels like a light flu. Once the parasite has retreated to its quiet cyst, a healthy person doesn’t notice it at all. It might seem as if Toxoplasma, in all its meekness, doesn’t warrant mention alongside parasites like trypanosomes and Plasmodium. But Toxoplasma actually manipulates the immune system of its host as elegantly as these other species do. If the parasite were to multiply madly, grinding up every cell in its host’s body, it would find itself inside a corpse rather than a living host. That would hardly be the sort of thing that a cat would want to hunt. Toxoplasma wants to keep its intermediate host alive, so it uses its host’s immune system to hold itself in check.
Toxoplasma does this with the exact opposite strategy as Leishmania. Leishmania pushes the immune system to make the T cells that help make antibodies. But Toxoplasma releases a molecule that tips the balance in favor of the inflammatory T cells. The inflammatory T cells rise up in huge numbers, turning macrophages into Toxoplasma assassins, hunting down the protozoa and blasting them apart. Only Toxoplasma that have hunkered down inside tough-walled cysts can survive the attack. From time to time, a few parasites break out of their cysts, squirting a fresh supply of their stimulating molecules, which reenergize the immune system like a booster vaccine. Roused again, the host’s macrophages drive the parasites back into their cysts. And so, thanks to Toxoplasma’s manipulations, its host stays healthy and able to fight disease while the parasite sits comfortably in its cyst, waiting to reach the promised land of a cat’s insides.
Toxoplasma becomes a threat to humans only when the cozy arrangement it creates falls apart. A fetus, for example, doesn’t have an immune system of its own. It is protected only by antibodies made by its mother that cross the placenta. The mother’s T cells are forbidden from crossing into the fetus, because they would act as if the fetus were a gigantic parasite and would kill it. Maternal antibodies do a good job against a flu virus or Escherichia coli bacteria, but they can’t protect against Toxoplasma. For that, the fetus would need inflammatory T cells to drive them into their cysts. As a result, it’s very dangerous for a woman to get a Toxoplasma infection during pregnancy. If the parasite manages to pass from her into her fetus, it will reproduce wildly. It will try to make the immune system rein it in, but inside the fetus there’s no audience to hear its calls. It simply proliferates until it causes massive, often fatal, brain damage.
In the 1980s, Toxoplasma became an accidental killer of another sort of human host: people suffering from AIDS. Human immunodeficiency virus, or HIV, the cause of AIDS, invades inflammatory T cells, using them to reproduce and killing them in the process. When Toxoplasma in a person with AIDS pops out of its cyst and divides, it expects a strong immune response to drive it back into hiding. But with hardly any inflammatory T cells left, its host is as helpless as a fetus. The parasite multiplies madly, causing much of its damage in the brain. Its host goes into a delirium and sometimes dies.
For over a decade, doctors could do almost nothing to stop the rampage of Toxoplasma in AIDS victims. But in the 1990s, scientists developed drugs that for the first time could slow down the replication of HIV and bring back the inflammatory T cells. In the relative few who can afford these drugs, Toxoplasma has gone gladly back into its lair, driven there by a healthy squad of T cells. But the millions who can’t afford these drugs continue to face madness brought on by this reluctant parasite.
Surviving the immune system is certainly difficult for a single-celled parasite, but at least it has the advantage of size. It can hide in the pockets of cells or the crooks of lymphatic ducts. The same can’t be said for parasitic animals. These multicellular creatures cross the radar of the immune system like vast dirigibles. They are as obvious as a transplanted lung. And without a continual supply of immune-suppressing drugs to hold off the immune system, a transplanted lung will die under its attack. Yet, parasitic animals, some sixty feet long, can live for years inside our bodies, feasting and breeding hundreds of thousands of young.
They thrive because they have many more ways of fooling our immune systems. One remarkable example is the tapeworm Taenia solium. Before the eggs of Taenia can turn into long ribbons in our bodies, they first need to spend some time in an intermediate host, usually a pig. The pig swallows the eggs with its food, and parasites hatch once they get to the intestines. They use enzymes to dig a hole in the intestines and wriggle their way out. Once they reach a capillary, they ride the bloodstream through the body to a muscle or an organ. There they disembark and settle down, growing into pearly marbles. They can wait for their final host in these cysts for years.
If pigs were the only places where tapeworms spent their cyst years, we’d probably know nothing about how they survive the immune system. But sometimes the eggs of Taenia solium end up in humans. (A person with a full-grown tapeworm inside him may get eggs on his hands and then make food for other people, for example.) The eggs proceed to act as if they’re in a pig: they hatch, and the larvae go through the same steps of breaking out of the intestines and finding a home somewhere in the body (often the eye or the brain). They then make a cyst, and depending on where they happen to settle, they may be harmless or fatal. If a tapeworm presses against blood vessels, it can kill off tissue; if it causes inflammation in the brain, it can trigger epileptic seizures. If it finds a safer spot, it may go unnoticed for years. But unlike Toxoplasma, which essentially falls asleep in its cyst, Taenia remains active inside its shell. Through little pores in the cyst wall it sucks in carbohydrates and amino acids, and it grows.