Researchers at Linköping University in Sweden have discovered a new kind of warning system that plays a role in the immune system. Mitochondria in the white blood cells produce a web of DNA fibers that act as a kind of alarm.
The mitochondrial web slinger
White blood cells (leukocytes) are a primary part of our immune system, and they help to defend us from the threat of disease. In the new study, the research team showed that several types of leukocytes react to the small DNA fragments, which resemble the DNA from bacteria and viruses. The leukocytes secrete a web made of mitochondrial DNA (mtDNA) strands.
This web sends signals to the surrounding cells that the body is under attack, which causes other leukocytes to release interferon type 1, a substance that helps the immune system to combat the infection. Previous studies have shown that blood mtDNA increases after trauma or inflammatory diseases; this study sheds new light on why this happens.
This not the first instance of such web-like structures being used in the immune system. Neutrophils, another type of immune cell, produce meshes coated with antibacterial proteins as a way of fighting infection. However, these mtDNA webs are considerably different from neutrophil meshes. The webs become active more quickly, within a couple of minutes. Neutrophil meshes do not produce a signal to other nearby cells to join the attack, and mtDNA webs remain in the blood system longer before they dissipate.
Too much of a good thing
Now that the researchers are aware of this alarm system, it raises the possibility of a therapy that can reduce the release of mtDNA and so reduce the inflammation it provokes.
But, surely, this mtDNA web system is a good thing; why would we want to reduce its activity?
It is, of course, a good thing that our immune system uses such mechanisms to defend us, but it is possible to have too much of a good thing. Sometimes, the defense system can be triggered unintentionally, such as after surgery or if the mtDNA is not removed from the blood. In this case, an undesirable inflammatory response may occur, and it is this unwanted side effect that the researchers seek to prevent.
High levels of interferon type 1, used as an alarm signal by the mtDNA webs, are observed in various autoimmune diseases and some types of cancer. The researchers believe that it may be possible to quantify the mtDNA webs to help interpret specific warning signals, leading to a better understanding of these diseases.
The discovery of this previously unknown defensive system from a cell component usually involved in energy production is intriguing. The more we learn about the immune system and ways to potentially control unwanted immune reactions and excessive inflammation, the better.
 Ingelsson, B., Söderberg, D., Strid, T., Söderberg, A., Bergh, A. C., Loitto, V., … & Rosén, A. (2018). Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C. Proceedings of the National Academy of Sciences, 201711950.