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23 September 2011Cornell University / PLoS Pathogens
How Toxoplasma gondii hijacks host immune cells
Cornell researchers recently discovered how T. gondii evades our defenses by hacking immune cells, making it the first known parasite to control its host's immune system. Immunologists from the College of Veterinary Medicine published the study in PLoS-Pathogens, describing a forced partnership between parasite and host that challenges common conceptions of how pathogens interact with the body.
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 study maps T. gondii's newfound ability to manipulate cells in the immune system at the molecular level.
When immune cells meet intruders, they release cytokines that summon more immune cells, which produce more cytokines, rapidly causing inflammation. "Toxoplasma hijacks immune cells to enforce a mutually beneficial balance," said Eric Denkers, professor of immunology. "We found that Toxoplasma quiets its host's alarm system by blocking immune cells from producing certain cytokines, proteins that stimulate inflammation. 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."
The study team then exposed immune cells in the lab to bacterial factors that typically stimulate the release of inflammatory cytokines. Cells infected with Toxoplasma produced no messages to trigger inflammation. The scientists found that Toxoplasma produces a specific protein called ROP16 to suppress inflammatory responses and that Toxoplasma sends ROP16 to infiltrate communication channels in immune cells, causing them to lower cytokine production.
"We are excited to have found the first non-bacterial pathogen able to exert this kind of control," said Denkers. "If Toxoplasma can do this, maybe other parasites can too. This is the first case where the whole process of immune system manipulation is close to being completely mapped out at the molecular level."
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Butcher BA, Fox BA, Rommereim LM, Kim SG, Maurer KJ, et al. (2011) Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog 7(9): e1002236. doi:10.1371/journal.ppat.1002236
