Study revealed- pathogens force immunity by using force
California: A study found that pathogens can use physical force to defeat the cell’s defense mechanisms. The study found that pathogens can avoid being swallowed by immune cells by exerting “propulsive force.” This force encases the pathogens in vacuoles that they cannot break down.
Researchers have uncovered a hitherto unknown mechanism by which infection physically infiltrates a cell, compromising the body’s immune defenses that prevent infection, much like a burglar would enter a home. Breaks the window for.
The discovery presents a potentially revolutionary approach to combating intracellular microorganisms that cause deadly infectious diseases such as chlamydia, malaria and tuberculosis. The Proceedings of the National Academy of Sciences published the work. Because the infections are protected inside host cells, these diseases are extremely difficult to treat.
“Using the parasitic Toxoplasma as our representative pathogen, our work shows that some intracellular pathogens can apply physical force during entry into host cells, which then allows the pathogens to escape degradation and survive intracellularly. allows,” said study lead author Yan Yu, professor in the chemistry department of the College of Arts and Sciences at IU Bloomington.
“This work suggests that targeting the mobility of pathogens could be a new way to tackle infections inside cells.”
Normally, 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 captured by the phagocyte and swallowed. is taken.
For pathogens that escape this process, it is generally thought that those pathogens must release a “secret arsenal” to “paralyze” the destructive machinery in the cell.
However, Yu’s study shows that this common belief is not true. He and his colleagues have found that pathogens can avoid entering immune cells by exerting “propulsive force.”
With this forced entry, pathogens are translocated into the vacuole which does not have the ability to break down these intruders. Vacuole is a reserve structure within a cell for storage and digestion.
To conduct the research, Yu and colleagues introduced the disease-causing parasite Toxoplasma into mouse-derived cells, and observed their behavior through a fluorescence microscope. These living parasites force their way into immune cells and proliferate.
The biggest challenge then was to determine whether the surviving parasite escaped immune defense with unknown chemical substances, or simply through force. To tackle this question, Yu and his team took an inventive approach: They created inactive parasites that can’t exert force or produce chemicals. Unlike living parasites, these “zombie” parasites rapidly destroyed the cell.
The researchers then used magnetic tweezers to push the inactive parasite into the immune cell to mimic the forceful entry seen in live Toxoplasma. The dormant parasite, now subject to simulated forced entry, survived the fall, similar to its living counterpart. This suggests that the force of entry, not the chemicals, explains the survival of the pathogen, Yu said.
To manipulate the parasite’s movement in the second experiment, researchers had to develop a “tweezer system” with magnetic nanoparticles. He also collaborated with a team at the University of Tennessee to develop computational models to simulate the behavior.
Additionally, the researchers conducted the same experiments using yeast to confirm that the mechanism observed could be found in other infectious agents, not just Toxoplasma.
“This study clarifies the contribution of physical forces to immune evasion and underscores the importance of targeting pathogen movement to combat intracellular infection,” Yu said. “We hope that this work may ultimately contribute to new efforts to fight a variety of infections that are harmful to human health.”
