One of the most intricate and fascinating aspects of physiology is the immune and inflammatory response and how it is triggered. At a 10,000 foot level, the immune system is triggered by the presence of some sign of an invading organism. Such a sign could come from, for example, detecting its genetic material through special receptors known as toll-like receptors (TLRs).
One such receptor, TLR-9, is used to detect foreign DNA sequences. These sequences, which are rare in vertebrates, are considered to be pathogen-associated molecular patterns (PAMPs). Once this process is started the result is systemic inflammation in order to quell the infection.
However, not all systemic inflammatory reactions are due to a microbial pathogen. The ICU is literally full of people who are exhibiting systemic inflammatory response syndrome (SIRS) but without a clinical infection. Trauma and post-surgical patients are two common examples. In these settings it is thought that tissue damage leads to the release of damage-associated molecular patterns (DAMPs), and not PAMPs, triggering the inflammation. A new paper from the Medical University of Vienna, elegantly provides more information to help unravel this process.
Within our cells are special structures that basically serve as the power plant, generating energy from oxygen: the mitochondria. Mitochondria are special amongst our cellular organelles as they were once free-living bacteria that entered into a symbiotic relationship with the evolutionary precursors to our cells and now live within our cells. As such, they retain their own genetic material which is, for all intents and purposes, bacterial.
Prior studies have demonstrated that mitochondrial DNA (mtDNA) levels correlate with illness severity in certain conditions such as trauma. In this fascinating study, this was taken one step further as the levels of circulating mtDNA as well as TLR-9 expression were measured in ICU patients. The findings show that high levels of mtDNA, when coupled with high TLR-9 expression, were found to correlate with mortality.
The study will likely lead to interest directed at medications to block TLR-9's effect but even without such an application the whole process is very interesting to ponder: little bacterial creatures that live within our cells and are essential for life leak their DNA into our blood when we are sick or hurt and, because of their ancestry, our body (quite understandbly) mistakes for a bacterial invasion and launches an attack which could be fatal for us.