DNA is essential to complex life – it is a complex set of instructions on how to build every protein in your body, from the signaling hormones in your head to the (unwanted) hairs on your feet.
But the code of life for us could well be the code of death for pathogens invading our bodies: a recently discovered process involves our immune cells trapping invaders in microscopic nets made of DNA.
But although this immune process is relatively new to science, it may be an extremely old method of fighting off infection. A new study by scientists from the UK reckons that it could be used by some of the most ‘ancient’ organisms on the planet, and have been preserved right through the evolutionary process.
So, what’s the point?
Our immune system is complex, with many different cells performing different tasks in order to prevent entry, slow down movement and ultimately destroy invaders such as bacteria and viruses. Different cells produce substances from bacteria-bursting antibodies to sticky mucous to contribute to this effort.
Some cells (neutrophils) are now known to generate nets of DNA. These neutrophil extracellular traps (which form the highly appropriate acronym, NETs) are thought to form a physical barrier to prevent movement of pathogens, but also contain anti-microbial chemicals to help kill them too.
Because NETs are a fairly recent discovery, their origins are still little-understood. The authors claim they have been observed in other mammals, as well as in birds and fish, but has not been ‘studied in detail’ in invertebrates.
A better understanding of what NETs are can help us not only to understand how they evolved, but also may help in understanding certain auto-immune diseases which are linked to NETs.
What did they do?
The authors of the paper reckoned that if NETs are indeed an ‘ancient’ defence system, then it would be used by creatures that evolved much earlier than vertebrates. So they ran tests on crabs, mussels and sea anemones to see if they deployed NETS too.
Certain immune cells were extracted from the creatures examined and certain chemicals, known to stimulate immune cells into responding were added to them.
A stain (dye that becomes visible when bound to specific chemicals) for DNA was also added. The stain cannot cross cell membranes so would only stain DNA in cells where the membrane was disrupted (i.e. dead cells) or DNA which was outside the cells.
To see how similar the immune cells’ reaction processes are to vertebrates, they also tested three different chemicals known to disrupt the production of NETs in mammals to see if they have the same effect in crabs (they didn’t test the other two).
Did they prove anything?
Stimulating the immune cells of the crabs ‘resulted in expulsion of material’ (a line worthy of the Bad Sex in Fiction Award) which stained positively (it just gets worse!) with the dye.
In addition, the material could be ‘dissolved’ with an enzyme used to break down DNA (DNAse-1). Similar observations were seen in the cells of the mussels and sea anemones too.
Electron microscope images of the ‘material’ reveal a ‘mesh’ structure ‘studded with small granules’, which they said was a ‘similar structure to mammalian NETS’, although with a few slight differences were noticed.
To show that this reaction is a genuine immune response, they added L. Anguillarum (an infectious bacterium to crabs) to the cells, which did indeed trigger the production of the same material.
They also found that the same chemicals known to disrupt NET production in mammals did the same in the crab cells.
So, what does it mean?
This is certainly evidence that NETs (or similar DNA-based defences) are used in invertebrates as well as vertebrates.
The authors argue that because the same chemicals were able to disrupt NET production in creatures as diverse as humans and crabs, it suggests that the immune response occurs by similar biochemical pathways.
This leads them to suggest that NETs are an ‘evolutionary ancient defence weapon’.
If this is the case, it would be interesting to see just how far up the evolutionary ladder NETs can be found – it seems like quite a generic response that could defend against a wide range of pathogens, so it may be the case that it is used by even simpler organisms than sea anemones.
If anything this shows how much in common we have with ancient organisms – many cellular processes and biochemicals have proven to be so successful that they have remained largely unchanged throughout evolution.
So perhaps it shouldn’t be such a surprise that a process which is one of the most important things an organism needs to do – protect itself – appears to also have stood the test of time.
Original article in Nature Communications Aug 2014
All images are open-source/Creative Commons licence.Credit: ynse (First); BruceBlaus (Second); Ar rous (Third); C T Robb et al. (Fourth); G Beard (Fifth)
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Find more articles like this in:
Robb C.T., Dyrynda E.A., Gray R.D., Rossi A.G. & Smith V.J. (2014). Invertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon., Nature communications, PMID: http://www.ncbi.nlm.nih.gov/pubmed/25115909
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