The highly contagious protozoa that infects more than half the world’s population evades the body’s defenses by hacking immune cells, making it the first known parasite to control its host’s immune system. Most of those infected are never free, or aware of, the intruders.
“Toxoplasma is an especially promiscuous parasite,” says Eric Denkers, professor of immunology at Cornell. “It infects nearly all warm-blooded species and much of the human population. Although it lives in vital brain and muscle tissues, it usually causes no obvious reaction.
Infection can seriously harm people with weak immune systems, yet most hosts experience no overt symptoms because Toxoplasma has found a way to coerce cooperation.”
Famous for its manipulative powers, T. gondii has been shown to alter the brain chemistry of rodents so that they fearlessly pursue cats. Cats eat the rodents, delivering the parasites to their breeding ground in feline intestines. Similar manipulations have surfaced in human studies linking T. gondii infections to behavioral and personality shifts, schizophrenia, and population variations, including cultural differences and skewed sex ratios.
The new study, reported in the journal PLoS Pathogens (DOI: 10.1371/journal.ppat.1002236), maps T. gondii’s newfound ability to manipulate cells in the immune system at the molecular level.
“We found that Toxoplasma quiets its host’s alarm system by blocking immune cells from producing certain proteins that stimulate inflammation,” says Denkers. “These proteins normally summon the immune system’s reinforcements, but if too many accumulate they can damage the body they’re trying to defend. An unregulated immune response can kill you (and the parasite).”
When immune cells meet intruders, they release these proteins that summon more immune cells, which produce more proteins, rapidly causing inflammation. T. gondii must allow enough of an immune response to keep its own numbers in check and ensure host survival, but not so many that it causes an overwhelming immune response that could kill the host (us) or eliminate the parasites (them).
“Toxoplasma hijacks immune cells to enforce a mutually beneficial balance,” Denkers explains. “Until recently we thought it walled itself away inside cells without interacting with its environment. It’s now clear that the parasite actively releases messages into cells that change cell behavior.”
To prove this, Barbara Butcher, working with Denkers, exposed immune cells in the lab to bacterial factors that typically stimulate the release of inflammatory proteins. “Cells infected with Toxoplasma produced no messages to trigger inflammation,” Denkers says. “Our colleagues at Stanford found that Toxoplasma produces a protein to suppress inflammatory responses. Collaborating with parasitologists at Dartmouth Medical School, we found that Toxoplasma sends this protein to infiltrate communication channels in immune cells, causing them to lower inflammatory response protein production.
Denkers adds “If Toxoplasma can do this, maybe other parasites can too. “This is the first case where the whole process of immune system manipulation by a parasite is close to being completely mapped out at the molecular level.”
Sleep well tonight knowing that Taxoplasma gondii parasites in your brain are balancing the inflammation response to their presence in your brain such that they don't kill you, and them, while they manipulate parts of your behavior. Another piece of information for those who believe that they are totally in control.
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