The research was conducted with the intracellular pathogen Toxoplasma as the model parasite. Credit: Science Photo Library
Key points:
- Like criminals forcing a door open or breaking a window, some dangerous pathogens invade the body through brute force.
- Using mouse-derived cells, researchers showed how some pathogens escape the phagocyte.
- The findings underscore the importance of targeting pathogen movement to combat intracellular infections.
Indiana University researchers have discovered a previously unknown process by which pathogens enter a cell with physical force, breaching the body's immune defenses that prevent infection.
Typically, when an invading pathogen encounters a phagocyte—a type of white blood cell responsible for destroying bacteria, viruses and other types of foreign particles—it is caught and ingested by the phagocyte. Pathogens that escape the phagocyte and go on to cause damage were thought to have a "secret arsenal" that paralyzes the degradative machineries in the cell to gain access.
However, this new study shows that is not true—the “secret arsenal” is really just a propulsive force that breaks down the immune cells’ barriers.
For the study, published in PNAS, researchers focused on the disease-causing parasite toxoplasma. They introduced the parasite into mouse-derived cells, observing their behaviors through a fluorescence microscope. Quickly, toxoplasma forcefully entered and thrived within immune cells.
But the question remained as to how they entered—by force, or an unknown immune defense? To find the answer, the scientists created inactivated parasites that cannot exert force or create chemical substances. Unlike live parasites, these “zombie” parasites were swiftly degraded in the cell.
The researchers then employed magnetic tweezers to push the inactivated parasite into the immune cell to mimic the forceful entry observed in live toxoplasma. The inactivated parasite, now subjected to simulated forceful entry, evaded degradation, akin to its live counterpart. This suggests that the force of entry—not chemicals—explains the pathogen’s survival.
In addition, the researchers conducted the same experiments using yeast to confirm that the mechanism observed could also be found in other infectious agents, not just toxoplasma. They say their research is a potential game-changer in the fight against intracellular pathogens responsible for causing infectious diseases such as tuberculosis, malaria and chlamydia. These diseases are notoriously difficult to treat because the pathogens are protected inside host cells.
“This study elucidates the contribution of physical forces in immune evasion and underscores the importance of targeting pathogen movement to combat intracellular infections,” said study lead author Yan Yu. “We’re hopeful this work may ultimately contribute to new efforts to fight a variety of infections that are harmful to human health.”