Pathogens use force to breach immune defenses, study finds: IU News
Creationists trying to defend their magic creator god argue that it didn't create pathogenic parasites and instead blame it on 'Sin'. Sadly for them, however, one of their leading cult gurus, Michael J. Behe, has pulled that rug from underneath them by writing a book in which he used the supposedly irreducibly complex flagellum of a common pathogen, Escherichia coli (E. coli) to argue that it must have been intelligently designed, (so God did it!). Behe's book, 'Darwin’s Black Box' is constantly being cited as 'proof' that the reputedly omniscience, omnipotent creator god of the Bible and Qur'an is real and creates things.
So, let's go with their 'proof of God' argument and assume therefore that pathogens are the intentional design of their putative designer god and were designed for the function they perform - making us sick, while producing more copies of themselves to make others sick too.
Now a team of researchers have shown the lengths this alleged designer god has gone to to continue making us sick and suffer. The team, led by Professor Yan Yu, of the College of Arts and Sciences’ Department of Chemistry, Indian University, Bloomington, IN, USA have shown that the intracellular pathogens like Toxoplasma, tuberculosis, malaria and chlamydia don't use subtlety to gain entry into the cell, probably because this would provoke an immune response as our immune system, allegedly designed by the same intelligent designer to protect us from the pathogens it designed to harm us, tried to fight back. Instead, they use brute force to break into the cell and once inside use the same force to break into a cell vacuole where they are protected by the internal cell membranes.
How the research team which included Professor Yan Yu's colleagues from Indiana University with Thomas K. Gaetjens and Steven M. Abel of the Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, TN, USA, made this discovery is explained in an Indian University new release:
Similar to a burglar breaking a window to get into a house, 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.
The work, published in the journal Proceedings of the National Academy of Sciences, introduces a potential game-changer in the fight against intracellular pathogens responsible for causing devastating infectious diseases, such as tuberculosis, malaria and chlamydia. These diseases are notoriously difficult to treat because the pathogens are protected inside host 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 caught and ingested by the phagocyte. For pathogens that escape this process, it is commonly thought that those pathogens must release a “secret arsenal” to “paralyze” the degradative machineries in the cell.Using the parasite Toxoplasma as our representative pathogen, our work shows that some intracellular pathogens can apply physical forces during their entry into host cells, which then allow the pathogens to evade degradation and to survive intracellularly. This work suggests that targeting the motility of pathogens may be a new way to combat infection inside cells.
Professor Yan Yu, lead author
College of Arts and Sciences’ Department of Chemistry
Indiana University, Bloomington, IN, USA.
However, Yu’s study shows that this common belief is not true. She and collaborators have found that pathogens can avoid being ingested within the immune cell by exerting a “propulsive force.” With this forceful entry, the pathogens are diverted into vacuoles that lack the ability to break down these infiltrators. A vacuole is a structure reserved for storage and digestion within a cell.
To conduct the research, Yu and colleagues introduced the disease-causing parasite Toxoplasma into mouse-derived cells, observing their behaviors through a fluorescence microscope. These live parasites forcefully entered and thrived within immune cells.
The biggest challenge then was to determine whether the live parasite escapes the immune defense with unknown chemical substances, or simply through force. To tackle this question, Yu and her team took an inventive approach: They 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, Yu said.
To manipulate the movement of the parasite in the second experiment, the researchers had to develop the “tweezer system” with magnetic nanoparticles. They also collaborated with a team at the University of Tennessee to develop computational models to simulate the behavior.This study elucidates the contribution of physical forces in immune evasion and underscores the importance of targeting pathogen movement to combat intracellular infections. We’re hopeful this work may ultimately contribute to new efforts to fight a variety of infections that are harmful to human health.
Professor Yan Yu.
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.
Other IU researchers on the study were first author Zihan Zhang, as well as Jin Ou, Yanqi Yu and Qiong Zhou. Additional co-authors are Thomas K. Gaetjens and Steven M. Abel at the University of Tennessee. This work was supported by the National Institutes of Health and the National Science Foundation.
From their paper in Proceedings of the National Academy of Sciences (PNAS):
SignificanceIt's time creationists stuck their head above the parapet on the question of pathogens and other parasites. How can they be Michael J Behe's supposed 'proof' that a creator god exists and not be the creation of that god? And, if they are the creation of that god, why should this not be regarded as evidence that their putative god is far from being the supposedly omnibenevolent god of the holy books, but a pestilential malevolence, forever designing ways to increase the suffering in the world?
Immune cells control infections by ingesting and degrading pathogens. However, some pathogens escape this defense mechanism to multiply inside host cells. While known evasion mechanisms involve virulence factors, many pathogens are mobile during invasion. How might the physical forces exerted by motile pathogens affect their degradative fate within the host? Here, we magnetically apply propulsive forces during cell entry of the parasite Toxoplasma and monitor its intracellular trafficking. By combining experiments and simulations, we demonstrate that propulsive forces from active cell entry hinder the phagocytic synapse assembly, diverting pathogens into a nondegradative trafficking pathway. This mechanism elucidates the contribution of physical forces in immune evasion and underscores the importance of targeting pathogen movement to combat intracellular infections.
Abstract
Phagocytosis is a critical immune function for infection control and tissue homeostasis. During phagocytosis, pathogens are internalized and degraded in phagolysosomes. For pathogens that evade immune degradation, the prevailing view is that virulence factors are required to disrupt the biogenesis of phagolysosomes. In contrast, we present here that physical forces from motile pathogens during cell entry divert them away from the canonical degradative pathway. This altered fate begins with the force-induced remodeling of the phagocytic synapse formation. We used the parasite Toxoplasma gondii as a model because live Toxoplasma actively invades host cells using gliding motility. To differentiate the effects of physical forces from virulence factors in phagocytosis, we employed magnetic forces to induce propulsive entry of inactivated Toxoplasma into macrophages. Experiments and computer simulations show that large propulsive forces hinder productive activation of receptors by preventing their spatial segregation from phosphatases at the phagocytic synapse. Consequently, the inactivated parasites are engulfed into vacuoles that fail to mature into degradative units, similar to the live motile parasite’s intracellular pathway. Using yeast cells and opsonized beads, we confirmed that this mechanism is general, not specific to the parasite used. These results reveal new aspects of immune evasion by demonstrating how physical forces during active cell entry, independent of virulence factors, enable pathogens to circumvent phagolysosomal degradation.
Zhang, Zihan; ; Gaetjens, Thomas K.; Ou, Jin; Zhou, Qiong; Yu, Yanqi; Mallory, D. Paul; Abel, Steven M.; Yu, Yan
Propulsive cell entry diverts pathogens from immune degradation by remodeling the phagocytic synapse
Proceedings of the National Academy of Sciences 120(49). DOI: 10.1073/pnas.2306788120
© 2023 PNAS.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.
Or is evolution by a mindless, natural process a better explanation which doesn't require the mental contortions of believing two diametrically opposite things simultaneously?
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