In response to the presence of the C. parvum parasite in the intestinal mucosa, the intestinal epithelial cells activate the immune system to detect the presence of the parasite.
The body needs to first sense an invasion; then it must send out signals to mobilize its energy to battle the invader. Growing information about these early stages of pathogen detection and response may help prevent various infectious diseases and inflammatory diseases of the immune system.
That was the target of the new study lead by researchers at the University of Pennsylvania School of Veterinary Medicine; it investigated the infection of the parasite Cryptosporidium.
When the researchers searched for the very first signals transmitted by a host infected with the parasite, they traced them not to an immune cell, as could be predicted, but to epithelial cells lining the intestine, where Cryptosporidium persists throughout the infection. These cells inside the gut, known as enterocytes , mediate the absorption of dietary nutrients, and they alert the body to danger through molecular receptor NLRP6, which is part of the inflammasome.
“You can think of the inflammasome as an alarm system in a house,” said Boris Striepen, a Penn Vet professor and senior author of the study, which was published in the journal Proceedings of the National Academy of Sciences. “It has various components – like a camera that watches the door and sensors on the windows – and once it’s activated, it amplifies those initial signals to warn of danger and send a call for help.
Cells also have these various elements, and we have shown the most detailed example of how a particular receptor in the gut detects a pathogen.
Usually, researchers have concentrated on immune cells including macrophages and dendritic cells, but this new discovery underscores that cells not normally considered part of the immune system – in this case, intestinal epithelial cells – play a significant role in how an immune response is initiated.
“There’s a growing body of literature that really appreciates what epithelial cells do to help the immune system recognize pathogens,” says Adam Sateriale, first author of the paper, who was a postdoctoral fellow in Striepen’s lab and now runs his own lab at the Francis Crick Institute in London. “They seem to be a first line of defense against infection.”
Striepen’s lab has focused on a major cause of diarrheal disease that can be fatal among young children in resource-poor settings.
Cryptosporidium, like most other waterborne disease causing microorganisms, is also causing half of all waterborne disease outbreaks in the United States.
It is known to cause distress among calves and stunt their development.
There is currently no vaccine or appropriate treatment available for these viruses.
In current work, Striepen, Sateriale, and their colleagues used a form of Cryptosporidium in mice that acts in several ways similarly to humans.
The researchers know that T cells regulate the parasite, but they wanted to know about the first steps of host-parasite interactions.
The one hint is the connection between malnutrition and infections caused by Cryptosporidium.
Early infection with Cryptosporidium and the resulting intestinal inflammation predisposes children to malnutrition and stunted growth; at the same time, children that are malnourished are more prone to infection.
Children who study and perform well are at lower risk for fatal infections.
The cause of this phenomenon is not well known.
“This got us thinking that perhaps some of the hazard recognition mechanisms that can trigger inflammation in the gut also play a role in the larger context of this infection,” Striepen adds.
These associations led the research team to investigate the Inflammasome and the impact it may have on the course of a bacterial infection.
They limit caspase-1’s operation by eliminating a key component of the inflammasome. “It turns out that he.”