Researchers can now explain how a cell that is being attacked by bacteria or viruses specifically manages to 'sound the alarm' among its neighboring cells so they can react with a quick response. Researchers published the research results in the journal Nature Microbiology.
In the study, researchers cultured cells exposed to the listeria bacteria which can cause the serious but rare type of food poisoning called Listeriosis.
In the petri dish, the researchers uncovered how the attacking listeria bacteria initially penetrated the cell, where they dumped a little of their DNA. The chunk of DNA was then distributed into the cytoplasm, which is the part of a cell that surrounds the cell nucleus. Here the protein cGAS discovered the foreign DNA, and along with the signal protein STING, sent alarm signals into the cell.
It is here that the newly-discovered messenger comes into the picture in the form of yet another protein, MVB12b, which is responsible for packing and exporting the DNA fragments in some fat bubbles called exosomes which resemble soap bubbles. They are then sent on to the neighbouring cell, where researchers have now documented that defensive responses can be started even before the cell is infected - with the protein simply being the unknown distributor. And this is important knowledge in the context of understanding, diagnosing and treating infectious diseases.
"This opens for the possibility of being able to 'turn up' the messenger so that it begins fighting the enemy even faster and can thus suppress the infection," says the senior author.
In the study, the research group also experimented with 'turning down' the messenger. This was done in experiments with mice who were given listeria bacteria while the researchers at the same time studied the effects of blocking the exosomes' possibility of sending signals between cells.
"When we did this, the mice found it difficult to quickly spread an immune signal and thereby send an alarm signal to the tissue that needed protecting. This provides new perspectives in relation to the treatment of autoimmune diseases such as Lupus, which leads to pain in the joints, skin rashes and severe renal impairment," says the senior author.
The author explains that autoimmune diseases are also characterised by the cell nucleus beginning to spit small DNA fragments out into the cytoplasm, or the cells having difficulty breaking down DNA from dead cells. DNA therefore accumulates in the cytoplasm, without any external bacteria or virus coming into play.
"Here, the immune system's cells simply start fighting themselves instead of an enemy from outside, and of course, this raises the question of whether it is possible to block the messenger mechanism that we've now found and mapped with these auto-immune diseases. For example, there is considerable interest in the question of whether blocking STING has an effect against autoimmune diseases such as Lupus," says the senior author.
https://www.nature.com/articles/s41564-019-0367-z?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+nmicrobiol%2Frss%2Fcurrent+%28Nature+Microbiology%29
The immune system's unknown messenger
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