A team of researchers has discovered the mechanisms that the Toxoplasma parasite uses to control the host’s immune system. By taking control of the immune response, the parasite can continue to live in the body’s cells undetected. The details are in a paper that was just published in the journal Structure.
Toxoplasmosis is a disease caused by the protozoan Toxoplasma gondii parasite. In the United States, more than 60 million people are estimated to carry the parasite. Toxoplasma gondii is incredibly common worldwide and transmitted through cat feces and contaminated food. There are no symptoms in most healthy patients and the parasite often goes undetected. Even when there are symptoms, they’re usually mild and include headaches, muscle soreness, and fever. Although the parasite doesn’t cause issues for most people, immunocompromised patients and pregnant women are at risk of developing serious side effects. Toxoplasmosis can kill an unborn fetus if the mother becomes infected, leading doctors to recommend that pregnant women avoid cleaning litterboxes. Toxoplasma is unusual in that it can suppress the immune response to the point of causing no symptoms but the molecular mechanisms behind this ability were unknown.
Researchers from the European Molecular Biology Laboratory and the Institute for Advanced Biosciences collaborated to study the structure and mechanisms of Toxoplasma parasites. Normally, when a parasite is detected by the body, a signaling pathway results in the activation of a protein called p38α. The protein then switches on the proper genes to start the body’s immune response. The research team found that Toxoplasma parasites hijack this response by attaching their own protein, called GRA24, to p38α. This method directly activates p38α and skips over the usual signaling pathways. GRA24 controls the host’s immune response, suppressing it, while also making it impossible for other proteins to interact with p38α. Toxoplasma can simply leave p38α activated but suppressed, allowing the parasite to remain hidden to the body.
The team’s findings provide new insights into how Toxoplasma can remain in the body undetected for long periods of time. The parasite hijacks the body’s natural immune response and keeps the signals suppressed. The team hopes that their study will aid in the development of anti-inflammatory drugs, which are currently designed to target p38α activity.
Pellegrini et al. Structural Basis for the Subversion of MAP Kinase Signaling by an Intrinsically Disordered Parasite Secreted Agonist. Structure (2016).