Researchers Decode Toxoplasmosis’ Control of Immune Cells

The infection toxoplasmosis is caused by the parasite Toxoplasma gondii and is widely spread. It is estimated that 30%-50% of the global human population are carriers. Cats are the parasites' main host, but the infection is also spread among other animals, including humans.

Toxoplasmosis is life-threatening to people with impaired immune systems and to unborn fetuses, but causes only mild symptoms in healthy individuals. However, there are studies showing that mental illnesses such as schizophrenia, depression and anxiety disorder are more common in people who are carriers of T. gondii.

Scientists collaborating with those at Stockholm University (Stockholm, Sweden) have shown how an obligate intracellular pathogen, T. gondii, takes advantage of a hitherto uncharacterized Ca2+ signaling axis in dendritic cells (DCs) to modulate the migration of parasitized host cells. They have demonstrated that the hypermigratory phenotype induced in DCs by T. gondii is predominantly dependent on the L-type voltage-dependent Ca2+ channel (VDCC) subtype Cav1.3, which is activated by γ-Aminobutyric acid (GABAergic) signaling upon T. gondii invasion.

The team found that by silencing of Cav1.3 by short hairpin RNA or selective pharmacological antagonism of VDCCs abolished the Toxoplasma-induced hypermigratory phenotype. In a mouse model of toxoplasmosis, VDCC inhibition of adoptively transferred Toxoplasma-infected DCs delayed the appearance of cell-associated parasites in the blood circulation and reduced parasite dissemination to target organs. The findings define a novel motility-related signaling axis in DCs and unveil those interneurons and DCs share common GABAergic motogenic pathways. T. gondii employs GABAergic non-canonical pathways to induce host cell migration and facilitate dissemination.

Antonio Barragan, PhD, a professor and the senior author of the study said, “We have decoded how the parasite takes control of immune cells, converting them into moving "zombies" which spread the parasite in the body. This helps us understand how the parasite is spread and disease occurs. In the longer term, it may help us develop targeted treatments for infection.” The study was published on December 7, 2017, in the journal Public Library of Science Pathogens.

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