PNAS paper detailed! When cryptosporidium invades, the intestinal cortical cells issue a danger alert through the subject NLRP6

December 30, 2020 // --- In order to fight infection effectively, the body first perceives that it has been invaded, and then the affected organization must signal that resources are gathered to fight the intruder.
to learn more about the early stages of identification and response of these pathogens may provide scientists with vital clues when preventing infections or treating inflammatory diseases caused by overactive immunity.
that's the intention behind a new study led by researchers from the University of Pennsylvania's School of Veterinary Medicine, which examined the infection of a parasite called Cryptosporidium.
When they looked for the first "dangerous" signals from hosts infected by the parasite, they did not trace the immune cells as expected, but instead tracked the skin cells in the intestines, where cryptosporidiums camped during the infection.
these intestinal cortectal cells take nutrients from the intestines, and in this study they found that they alerted the body to danger through the molecular subject NLRP6, an integral part of the inflammatory body (inflammasome).
study was published in the January 12, 2021 issue of the journal PNAS under the title "The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6".
the pattern of cryptosporidium activating inflammatory bodies, pictured is PNAS, 2020:10.1073/pnas.2007807118.
think of inflammatory bodies as alarm systems in the house," said Dr. Boris Striepen, author of the paper and a professor in the Department of Pathology biology at the University of Pennsylvania School of Veterinary Medicine.
it has components, such as a camera on the observation door and sensors on the window -- once triggered, it amplifies the initial signal to warn of danger and send out a distress signal.
cells also have these different compositions, and now we have provided perhaps the clearest example yet of how a particular subject in the gut works as an important sensor protein for the perception of intestinal infections.
Usually, attention is focused on immune cells, such as macrophages and degenerative cells, because they are the first cells to detect foreign invaders, but these new findings highlight cells that are not normally considered part of the immune system ---super study refers to intestinal epithelocyte cells--- which play a key role in how the immune response starts, Striepen said.
, lead author of the paper, said, "There is a growing body of literature that really understands what corted cells do to help the immune system perceive pathogens.
seem to be the first line of defense against infection.
" Striepen laboratory has invested considerable attention in cryptosporidium, the main cause of diarrhoeal diseases, which can be fatal to young children in resource-poor areas of the world.
are also a threat to people in well-resourced environments, causing half of all water-borne disease outbreaks in the United States.
in veterinary science, it is known for infecting calf, which hinders its growth.
there is no effective treatment for these infections and no vaccine.
the new study, Striepen, Sateriale and colleagues used a naturally occurring species of mouse cryptosporidium, which they recently found could in many ways simulate human infections.
the researchers knew that T-cells helped control the parasite in the later stages of infection, they began looking for clues as to what happened in the first place.
important clue is the unfortunate link between malnutrition and cryptosporidium infection.
early infection with cryptosporidium and associated intestinal inflammation, which can lead to malnutrition and stunting in children, while malnourished children are more vulnerable to infection.
can lead to worsening conditions and put children at greater risk of fatal infection.
mechanism behind this phenomenon is not yet clear.
Added, "It makes us think that perhaps some of the dangerous sensing mechanisms that drive inflammation in the gut also play a role in the context of this infection."
", the researchers studied inflammatory bodies and their effects on infection processes in mouse models in more detail.
they do this by removing a key component in the inflammatory body--- an enzyme called caspase-1--- an enzyme.
, "It turns out that mice without this enzyme have much higher levels of infection, " said Sateriale, a senior at the hospital.
further studies have shown that mice that lack caspase-1 in intestinal endocyst cells alone suffer from the same level of infection as mice that completely lack it in the body, confirming that intestinal endocyst cells play a key role.
with this idea, the researchers found that in a variety of candidate receptors, only the loss of NLRP6 receptors can cause this parasitic infection out of control.
NLRP6 is a subject confined to the supersethic barrier that has previously been associated with the perception and maintenance of the gut microbiome (naturally planted bacteria).
However, the experiment found that mice that had never been exposed to bacteria and therefore lacked a microbiome also activated their inflammatory bodies when infected with cryptosporidium--- suggesting that this aspect of the warning signal occurred in a direct response to the parasitic infection, regardless of the gut bacterial community.
to track how triggering an inflammatory body leads to an effective response, the researchers looked at signaling molecules or cytokines that are usually associated with inflammatory body activation.
they found that the infection led to the release of IL-18, and that mice that lacked the cytokine or the ability to release it showed more serious infections.
when you rejoin IL-18, you can save the mice," said Sateriale, who almost reversed the effects of the infection.
, Sateriale and their colleagues believe there is still a lot of research to be done to find a vaccine against cryptosporidium.
, however, say their findings help shed light on important aspects of the interaction between the parasite, the immune system and the inflammatory response.
Looking ahead, they are exploring the later stages of cryptosporidium infection to see how the host successfully suppresses it.
now we understand how infections are detected, and we want to understand how they are controlled," said Sateriale, a government source at the hospital.
the immune system perceives the parasites, how do they limit their growth and kill them? (Bioon.com) Reference: 1. Adam Sateriale el al. The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6. PNAS, 2020:10.1073/pnas.2007807118.2.Gut cells sound the alarm when parasites invade