Summary: Stockholm University researchers have discovered how a common parasite found in cat feces moves through the body and enters the brain. Toxoplasma gondii is able to take control of immune cells and use them to move through the body, eventually reaching the brain.
Source: Stockholm University.
Scientists have previously shown that a parasite from cats can infect people’s brain and affect our behaviour. Now, researchers at Stockholm University have discovered how the parasite takes control of our cells.
“We have decoded how the parasite takes control of immune cells, converting them into moving “zombies” which spread the parasite in the body,” said Antonio Barragan, professor at Stockholm University and one of the authors of the new study.
The infection toxoplasmosis is caused by the parasite Toxoplasma gondii and is widely spread. It’s estimated that 30–50 per cent of the global human population are carriers. Cats are the parasites’ main host, but the infection is also spread among other animals, including humans. A series of studies have previously shown that the parasite affects the brain of infected rats so that they lose fear of cats and even become attracted to cats’ smell, making them an easy prey. This is how the parasite is spread onward, by ensuring that the rat is eaten by a cat. Toxoplasmosis is life-threatening to people with impaired immune systems and to unborn foetuses, 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 Toxoplasma gondii. There are also studies indicating that the parasite may affect aggressive or risky behaviour.
Cells become Trojan horses
Researchers at Stockholm University have now been able to show how the parasite takes control and force immune cells around the body to spread it, eventually reaching the brain. When we become infected with Toxoplasma, for example by eating insufficiently cooked meat or by contact with cat faeces, the parasite ends up in the stomach. It then passes through the intestinal wall and is met by immune cells that would normally kill it. Instead, immune cells become “Trojan horses”. By secreting the substance GABA, they can spread the infection into the body.
“Is it a coincidence or evolution? It resembles how nerve cells speak to each other in our brains”, said Antonio Barragan.
Can be inhibited by blood pressure medicine
The new research has shown that the small calcium molecule is the messenger in the communication. The researchers have found a new calcium receptor on immune cells, acting as a mailbox to receive the parasite’s orders for the cell to move.
“The neat thing is that the signal can be inhibited by regular blood pressure medicine. When mice received the medicine, the spread of the parasite was inhibited. We do not want to say that blood pressure medicine can cure toxoplasmosis, but we have discovered a new signalling pathway in immune cells that is linked to their motility and that the parasite utilizes in a very smart way. 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,” said Antonio Barragan.
Source: Stockholm University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the Stockholm University video.
Video Source: Video credited to Stockholm University.
Original Research: Full open access research for “Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii” by Sachie Kanatani, Jonas M. Fuks, Einar B. Olafsson, Linda Westermark, Benedict Chambers, Manuel Varas-Godoy, Per Uhlén, and Antonio Barragan in PLOS Pathogens. Published online December 7 2017 doi:10.1371/journal.ppat.1006739
[cbtabs][cbtab title=”MLA”]Stockholm University “How Toxoplasmosis Exploits Immune Cells to Reach the Brain.” NeuroscienceNews. NeuroscienceNews, 8 December 2017.
<https://neurosciencenews.com/immune-cells-toxoplasmosis-8142/>.[/cbtab][cbtab title=”APA”]Stockholm University (2017, December 8). How Toxoplasmosis Exploits Immune Cells to Reach the Brain. NeuroscienceNews. Retrieved December 8, 2017 from https://neurosciencenews.com/immune-cells-toxoplasmosis-8142/[/cbtab][cbtab title=”Chicago”]Stockholm University “How Toxoplasmosis Exploits Immune Cells to Reach the Brain.” https://neurosciencenews.com/immune-cells-toxoplasmosis-8142/ (accessed December 8, 2017).[/cbtab][/cbtabs]
Abstract
Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii
The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon T. gondii-infection, ?–aminobutyric acid (GABA)/GABAA receptor signaling triggers a hypermigratory phenotype in dendritic cells (DCs) by unknown signal transduction pathways. Here, we demonstrate that calcium (Ca2+) signaling in DCs is indispensable for T. gondii-induced DC hypermotility and transmigration in vitro. We report that activation of GABAA receptors by GABA induces transient Ca2+ entry in DCs. Murine bone marrow-derived DCs preferentially expressed the L-type voltage-dependent Ca2+ channel (VDCC) subtype Cav1.3. 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 present data establish that T. gondii-induced hypermigration of DCs requires signaling via VDCCs and that Ca2+ acts as a second messenger to GABAergic signaling via the VDCC Cav1.3. The findings define a novel motility-related signaling axis in DCs and unveil that interneurons and DCs share common GABAergic motogenic pathways. T. gondii employs GABAergic non-canonical pathways to induce host cell migration and facilitate dissemination.
“Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii” by Sachie Kanatani, Jonas M. Fuks, Einar B. Olafsson, Linda Westermark, Benedict Chambers, Manuel Varas-Godoy, Per Uhlén, and Antonio Barragan in PLOS Pathogens. Published online December 7 2017 doi:10.1371/journal.ppat.1006739
