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Toxoplasma gondii persuades immune cells to change behavior and help spread

Toxoplasma gondii persuades immune cells to change behavior and help spread

 


A study by Stockholm University researchers shows how a microscopic parasite carried by a large portion of the world’s population can successfully spread through the body, reach the brain, and cause life-threatening encephalitis. The team’s research shows how toxoplasma gondii It can infect macrophage immune cells, effectively hijacking their identity and making them behave like dendritic cells (DCs). The scientists suggested their findings could point to new strategies for the development of cell therapies.

“We have discovered a protein that the parasite uses to reprogram the immune system,” said Dr. Arne Ten Hoov, a researcher in the Department of Molecular Biology at the Wenner-Gren Institute at Stockholm University.The team reported their findings Cell hosts and microorganismsin a paper titled “”of toxoplasma The effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages’, they said: T. Gondi Allowing normally sessile macrophages to acquire the migratory functions normally attributed to DCs. “

T. Gondi is probably the most common human parasitic infection worldwide, the authors suggest, citing estimates that it “encounters one-third of the world’s population.” T. Gondi for a lifetime. “Most healthy infected people don’t know they’re carriers. In fact, the parasite also infects many animal species, including pets. All felines, not just domestic cats, play a central role in their life cycle. toxoplasmaBecause the parasite can reproduce sexually only in the intestines of cats. In other hosts, such as humans, dogs, or birds, reproduction is by parasite division.

toxoplasma It spreads through food and contact with cats. In nature, it spreads preferentially among cats and rodents. The parasite can lie dormant in the rodent’s brain, and when the cat eats the rodent, the parasite multiplies in the cat’s gut and enters the environment through the cat’s droppings. Rodents that eat plants or other materials that may have cat feces on them can become infected. Humans become infected by eating meat or coming in contact with cat feces.

of toxoplasma Parasites can cause a disease called toxoplasmosis. When a person is first infected, they will have mild symptoms similar to those of a cold or the flu. The parasite spreads throughout the body. “Following an oral infection, T. Gondi It spreads widely from the gut and reaches peripheral organs such as the central nervous system,” the researchers wrote.

Then, after the initial infection phase, the parasite transitions to a dormant or sleeping stage in the brain, initiating a chronic, silent infection that can last for decades or even a lifetime. It causes no symptoms in healthy people, but can cause life-threatening brain infections in people with weakened immune systems, such as HIV-infected people, organ transplant recipients, and patients undergoing chemotherapy. and may be dangerous to the fetus. pregnant. Eye infections can develop in otherwise healthy people.

To fight infections, the various roles of immune cells in the body are very tightly regulated.Scientists have long wondered toxoplasma It infects a large number of people and animal species and spreads very efficiently. The authors noted that studies in mice have shown that dendritic cells can act as a ‘Trojan horse’. T. Gondi Spread. “DC can act as a ‘Trojan horse’. T. Gondi Transmission to mice in a manner related to parasite genotype. So, when DCs are invaded by parasites, they are induced to migrate.

A newly reported study showed that parasites can make macrophages behave like migratory dendritic cells. Result is, T. Gondi Effectively injecting the effector protein GRA28 into the nuclei of parasitic macrophage immune cells, affecting gene transcription in the host cell, effectively tricking it into acting as if it were a dendritic cell and promoting migratory behavior and allows the parasite to spread throughout the body. “Following an oral infection, T. Gondi We encounter sessile macrophages in the gut and other peripheral tissues,” they wrote. ” … Moreover T. Gondi Upon infection, macrophages initiate the expression of transcription factors normally attributed to DCs …infection resulted in a transcriptional signature consistent with the acquisition of DC-like migratory properties …the dissemination of T. Gondi Intestinal infection is rapid, asymptomatic, and has no systemic inflammation….”

Image shows immune cells infected with Toxoplasma gondii parasites (red).The surface of the cell is colored green and the nucleus of the cell is colored blue [Antonio Barragan].

This study provided a molecular explanation for this phenomenon and showed that the parasites are much more targeted and spread than previously thought. “…we identified the parasite effector GRA28 as a mediator of upregulation of CCR7 expression and chemotaxis in parasitic macrophages…macrophage migratory responses influenced parasite dissemination in mice.” rice field.”

The work was led by Dr. Antonio Barragán, in collaboration with researchers in France and the United States.”It’s amazing that a parasite can hijack an immune cell’s identity in such a clever way,” Barragan said. “We believe our findings explain why.” toxoplasma Once infected in humans and animals, it spreads very efficiently in the body. “

The authors conclude that: T. Gondi Exploiting the migratory plasticity of parasitized macrophages to promote their dissemination…This finding reveals a putative alternative pathway by which mononuclear phagocytes can be migrated or activated .

Sources

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2/ https://www.genengnews.com/parasitic-diseases/toxoplasma-parasite-persuades-immune-cell-to-change-behaviour-aiding-dissemination/

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