Unintelligent Malevolence
The Ludicrous Complexity of Arms Races Between Parasites and Hosts
Image: The Brodsky Laboratory
The Ludicrous Complexity of Arms Races Between Parasites and Hosts
Researchers from Penn Vet observed, for the first time, an intestinal pyogranuloma, formed in response to Yersinia infection. The organized grouping of cells includes monocytes (in green), neutrophils (in magenta), and Yersinia
bacteria (in white), and depends on monocytes to form and to control infection, the team found.
Image: The Brodsky Laboratory
Peyer's Patches - organized lymphoid nodules commonly found in the small intestines.
Hard though it is to imagine any intelligent adult holding to such beliefs, Creationists believe that parasites were intelligently designed to make us sick and the same designer gave us an immune system to help stop parasites doing what it designed them to do. It then indulged in a pointless arms race with itself to try to make sure both parasites and our immune system did what they were designed to do.
It's as though the creator is some hate-filled but incompetent, schizophrenic amnesiac, intent on harming us one day and protecting us the next, but not remembering what it was trying to do yesterday and treating its solutions to problems yesterday as problems to be solved today, and no real idea about the basic principles of design.
Now researchers at the University of Pennsylvania School of Veterinary Medicine (Penn Vet) have discovered how this arms race has resulted in a continuous battle in or intestines between our immune system and bacteria if the Yersina genus which includes the plague organism, Y. pestis.
The setting for creationism's putative designer's ludicrous battle with itself is the host's intestines where the Yersinia organisms, which are designed to overcome the body's first line of defences, set up colonies in the lymph system. The lymph system's purpose is to protect us from these sorts of infections but the pathogens have been designed to use the system against us!
The body's response is to then try to seal in these colonies with a collection of immune cells to form a granuloma, sustained by monocytes.
The problem is this solution doesn't always work as designed and the granulomas break down when the monocytes fail to sustain them. The infection can ten enter the blood stream and cause serious illness.
The research and its significance is described in a news release from Penn Vet:
Yersinia bacteria cause a variety of human and animal diseases, the most notorious being the plague, caused by Yersinia pestis. A relative, Yersinia pseudotuberculosis, causes gastrointestinal illness and is less deadly, but naturally infects both mice and humans, making it a useful model for studying its interactions with the immune system.Regrettably, the team's research paper in Nature Microbiology is behind a paywall:
These two pathogens, as well as a third close cousin, Y. enterocolitica, which affects swine and can cause food-borne illness if people consume infected meat, have many traits in common, particularly their knack for interfering with the immune system’s ability to respond to infection.
The plague pathogen is blood-borne and transmitted by infected fleas. Infection with the other two depends on ingestion. Yet the focus of much of the work in the field had been on interactions of Yersinia with lymphoid tissues, rather than the intestine. A new study of Y. pseudotuberculosis led by a team from Penn’s School of Veterinary Medicine and published in Nature Microbiology demonstrates that, in response to infection, the host immune system forms small, walled-off lesions in the intestines called granulomas. It’s the first time these organized collections of immune cells have been found in the intestines in response to Yersinia infections.
The team went on to show that monocytes, a type of immune cell, sustain these granulomas. Without them, the granulomas deteriorated, allowing the mice to be overtaken by Yersinia.
The findings have implications for developing new therapies that leverage the host immune system, Brodsky says. A drug that harnessed the power of immune cells to not only keep Yersinia in check but to overcome its defenses, they say, could potentially eliminate the pathogen altogether.Our data reveal a previously unappreciated site where Yersinia can colonize and the immune system is engaged. These granulomas form in order to control the bacterial infection in the intestines. And we show that if they don’t form or fail to be maintained, the bacteria are able to overcome the control of the immune system and cause greater systemic infection.
In all three Yersinia infections, a hallmark is that they colonize lymphoid tissues and are able to escape immune control and replicate, cause disease, and spread.
Because it’s an orally acquired pathogen, we were interested in how the bacteria behaved in the intestines. Daniel [Sorobetea, first-author] made this initial observation that, following Yersinia pseudotuberculosis infection, there were macroscopically visible lesions all along the length of the gut that had never been described before.
We hypothesize that it’s a general role for the monocytes in other tissues as well.
Previous to this study we knew of Peyer’s patches to be the primary site where the body interacts with the outside environment through the mucosal tissue of the intestines.
These therapies have caused an explosion of excitement in the cancer field, the idea of reinvigorating the immune system. Conceptually we can also think about how to coax the immune system to be reinvigorated to attack pathogens in these settings of chronic infection as well.
Professor Igor E. Brodsky, senior author
Robert R. Marshak Professor and chair of the Department of Pathobiology
University of Pennsylvania School of Veterinary Medicine.
Pennsylvania, USA.
A novel battlefield
Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica share a keen ability to evade immune detection.
Earlier studies had shown that Yersinia prompted the formation of granulomas in the lymph nodes and spleen but had never observed them in the intestines until Daniel Sorobetea, a research fellow in Brodsky’s group, took a closer look at the intestines of mice infected with Y. pseudotuberculosis.
The research team, including Sorobetea and later Rina Matsuda, a doctoral student in the lab, saw that these same lesions were present when mice were infected with Y. enterocolitica, forming within five days after an infection.
A biopsy of the intestinal tissues confirmed that the lesions were a type of granuloma, known as a pyogranuloma, composed of a variety of immune cells, including monocytes and neutrophils, another type of white blood cell that is part of the body's front line in fighting bacteria and viruses.
Granulomas form in other diseases that involve chronic infection, including tuberculosis, for which Y. pseudotuberculosis is named. Somewhat paradoxically, these granulomas—while key in controlling infection by walling off the infectious agent—also sustain a population of the pathogen within those walls.
The team wanted to understand how these granulomas were both formed and maintained, working with mice lacking monocytes as well as animals treated with an antibody that depletes monocytes. In the animals lacking monocytes “these granulomas, with their distinct architecture, wouldn’t form,” Brodsky says.
Instead, a more disorganized and necrotic abscess developed, neutrophils failed to be activated, and the mice were less able to control the invading bacteria. These animals experienced higher levels of bacteria in their intestines and succumbed to their infections.
Groundwork for the future
The researchers believe the monocytes are responsible for recruiting neutrophils to the site of infection and thus launching the formation of the granuloma, helping to control the bacteria. This leading role for monocytes may exist beyond the intestines, the researchers believe.
But the discoveries also point to the intestines as a key site of engagement between the immune system and Yersinia.
Peyer’s patches are small areas of lymphoid tissue present in the intestines that serve to regulate the microbiome and fend off infection.
In future work, Brodsky and colleagues hope to continue to piece together the mechanism by which monocytes and neutrophils contain the bacteria, an effort they’re pursing in collaboration with Sunny Shin’s lab in the Perelman School of Medicine’s microbiology department.
A deeper understanding of the molecular pathways that regulate this immune response could one day offer inroads into host-directed immune therapies, by which a drug could tip the scales in favor of the host immune system, unleashing its might to fully eradicate the bacteria rather than simply corralling them in granulomas.
Abstract Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signalling and immune defence, inducing neutrophil-rich pyogranulomas (PGs) within lymphoid tissues. Here we uncover that Yp also triggers PG formation within the murine intestinal mucosa. Mice lacking circulating monocytes fail to form defined PGs, have defects in neutrophil activation and succumb to Yp infection. Yersinia lacking virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst do not induce PGs, indicating that intestinal PGs form in response to Yp disruption of cytoskeletal dynamics. Notably, mutation of the virulence factor YopH restores PG formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes override YopH-dependent blockade of innate immune defence. This work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation.I doubt that any Creationist would have the courage to read this far, but this offer is open to any who do: Please explain how this system can be regarded as the work of an omnibenevolent, omniscience, intelligent designer and not the work of either an incompetent malevolence or the result of amoral, utilitarian natural processes operating without a plan.
Sorobetea, Daniel; Matsuda, Rina; Peterson, Stefan T.; Grayczyk, James P.; Rao, Indira; Krespan, Elise; Lanza, Matthew; Assenmacher, Charles-Antoine; Mack, Matthias; Beiting, Daniel P.; Radaelli, Enrico; Brodsky, Igor E.
Inflammatory monocytes promote granuloma control of Yersinia infection
Nature Microbiology (2023); DOI: 10.1038/s41564-023-01338-6
© 2023 Springer Nature Ltd.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.
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