The intestinal cells become alert on the attack of the parasite, the study said – Health

The intestinal cells become alert on the attack of the parasite, the study said – Health

Researchers at the School of Veterinary Medicine found that cells lining the gut are capable of combating the parasite Cryptosporidium with the help of a self-produced chain reaction.

To effectively combat an infection, the body first realizes that it has been attacked, then the affected tissue must send signals from coral resources to fight the intruder. Knowing more about these early stages of pathogen identification and response can provide scientists with important clues when it comes to preventing infections or treating inflammatory diseases resulting from overactive immunity.

This was the intent behind a new study led by researchers at the Pennsylvania School of Veterinary School investigating infections with the parasite Cryptosporidium. When the team looked for the very first “danger” signals emitted by a host infected with the parasite, they discovered them not in an immune cell, as might have been expected, but for epithelial cells lining the intestines, where An infection that sets up the Cryptocidium store.

Known as enterocytes, these cells carry nutrients from the gut, and here they were shown to alert the body to danger through the molecular receptor NLRP6, known as the enflamasum Is a component.

“You can think of InflameSam as an alarm system in a house,” says Boris Strippen, a professor in the Department of Pathobiology in Penn Strait and senior author on the paper, who is publishing in the Journal of the National Academy of Sciences . . “It has various components – such as a camera that sees the door, and sensors on the windows – and once triggered it amplifies the first signals that warn of danger and send a call for help.

Cells have these different components, and now we have given a clear example of how a particular receptor in the intestine acts as a sensor for an important intestinal infection. “Typically, Strypen says, researchers have focused on immune cells. , Like macrophages and dendritic cells, as the first to detect foreign invaders, but this new finding underscores that cells are not usually thought of as part of the immune system – in this case the intestines. Epithelial cells are playing an important role in how the immune response begins.

“There is a growing body of literature that is really appreciating what epithelial cells are doing to help the immune system sense pathogens,” says Adam Strette, the first author on the paper who was a postdoc in Strippen’s laboratory and Now leads his laboratory at the Francis Crick Institute in London. “They appear to be the first line of defense against infection.”

Strippen’s laboratory has paid considerable attention to Cryptosporidium, a major cause of diarrheal disease that can be fatal in young children in resource-poor areas around the world. Cryptosporidium is also a threat to people in well-regenerated environments, causing half of all water-borne diseases in the United States. In veterinary medicine, it is known to infect calves, stunting their growth. There is no effective treatment for these infections nor is there any vaccine.

In the present work, Strypen, Siste, and colleagues took advantage of a naturally occurring species of mouse Cryptosporidium that they recently mimicked in many cases of human infection. While researchers knew that T cells help control the parasite in the later stages of infection, they started looking for clues to what happens earlier.

An important clue is the unfortunate relationship between malnutrition and Cryptosporidium infection. Early infection with Cryptosporidium and inflammation of the gut that goes with it predicts malnutrition and stunted growth in children; At the same time, children who are malnourished are more susceptible to infection. This increases the risk of life-threatening infections in children, which can lead them downstream. The mechanism behind this phenomenon is not well understood.

“This led us to think that perhaps some dangerous-sensing mechanisms that can cause inflammation in the gut may also play a role in the larger context of this infection,” says Stripe. Inflammation and its effect on the course of infection in their mouse model. They did this by removing a key component of the inflamasome, an enzyme called caspase-1. “It turns out that the animals who are missing it had a much higher infection level,” says Cittete.

Further work suggests that only caspase-1 deficient mice in the intestinal epithelial cells suffered from infection because they are completely deficient, demonstrating an important role of the epithelial cell.

Consistent with this view, the team led by Penn Vet showed that, of the various types of candidate receptors, only the loss of the NLRP6 receptor leads to failure to control infection. NLRP6 is a receptor associated with epithelial barriers, which have previously been associated with colonization of intestinal microbiomes, bacteria, and naturally occurring glands. However, experiments showed that mice never exposed to bacteria, and thus lacking a microbiome, also activated their inflammation upon infection with Cryptosporidium – a sign that this aspect of the danger signal The parasite occurs in direct response to infection and independent of the intestinal bacterial community.

To find out how the intestinal inflammation reacted effectively, researchers looked at some of the signaling molecules, or cytokines, that are typically associated with inflamosome activation. They found that infection leads to the release of IL-18, with animals that lack this cytokine or have the ability to release it from more severe infections. “And when you add the IL-18 back, you can save these mice,” Siste says. , Almost reversing the effects of infection.

Strippen, Suntet, and colleagues believe that much work has to be done to find a vaccine against Cryptosporidium. But they say that their findings help highlight important aspects of the difference between parasites, the immune system, and the inflammatory response, relationships that may inform these translational targets.

Moving forward, they are looking at the later stages of Cryptosporidium infection to see how the host successfully succumbs to it. “Now that we understand how an infection is detected, we want to understand the mechanisms by which it is controlled,” says Satorre. “After the system senses a parasite, what is done to restrict their growth and kill them?”

(This story is published from a wire agency feed without textual modifications.)

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