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After a lot of blogging about our lifes as scientists and the latest science news, it is time to go back to the basics. And what would be better than me telling you the 10 reasons why I think macrophages are the best cells ever?
- Macrophages are omnipresent – like every good rock star. They are in every tissue of your body – your skin, liver, heart, lung and brain. As macrophages belong to our first line of defense against pathogens, it is crucial that they are present in all tissues to surveil them for possible infections.
- Macrophages are not the same in every tissue. Sure, their main immunological function is to defend the tissue they are in against infections and that’s the same in every tissue.
- Macrophages also have tissue-specific functions. Brain macrophages, for example, are called microglia and form connections with neurons to check if they are happy. If these connections break off, for example due to injury or degeneration (such as in Alzheimer’s disease), microglia get activated. This is very different to the other organs where the cells get activated by stimuli not by the loss of stimuli!
- Macrophages have life figured out – I mean the main thing they do is eat! Macrophage even means big eater in Greek.
- Macrophages eat all dead cells they come across and that means they can facilitate wound healing. They clear damaged tissue and produce factors that induce the formation of new blood vessels. Macrophages also lay down a new extracellular matrix to allow the tissue to re-grow. Along similar lines scientists have shown that macrophages play a role in limb regeneration in salamanders. They found that removing macrophages from the animal resulted in failure of limb regeneration and tissue scarring instead!
- The main role macrophages have is eating infiltrating pathogens. Once taken up by the macrophage, the intruder is chewed up into little pieces called peptides. These peptides are then presented on the surface of the cell in order to activate the second arm of the immune system – the adaptive immune system. Macrophages are team players! And who doesn’t like a team player?
- Adaptive immune cells, both T and B cells carry highly specific receptors on their surface. These receptors can recognise a piece from a certain pathogen – called antigen. When the cells meet their antigen they get activated, multiply and effectively attack the pathogen. This is great. But also limiting – as every cell only recognises one piece of one pathogen. Macrophages are more well-rounded – they carry so called pattern recognition receptors which bind to molecules that are commonly found on lots of bacteria or viruses. Making them the perfect first line of defense. So if I had to choose between either a macrophage and a T cell, I’d rather have a macrophage so my chances of catching the intruder are higher!
- Sometimes macrophages get in over their head. One example for this is Tuberculosis, a bacterium, which infects macrophages and lives inside them. Once non-infected macrophages notice an infected macrophage they shield it to contain the intruder. They form an organised structure of macrophages and other immune cells called granuloma. While the idea of shielding the infected cell and thereby preventing the spreading of the bacteria is good, it also does not allow the macrophages to present the bacteria to the adaptive immune system meaning no effective immune response can be mounted. Interestingly, the middle of the granuloma is formed by a giant-cell, which is a macrophage with several cell nuclei. These cells are formed by incomplete cell division – meaning that the DNA duplicates but stays within the same cell. These giant-cells are massive producers of cytokines and can live much longer than normal macrophages.
- Some macrophage populations are in your body from before you were born! It has been shown that microglia migrate into the developing brain of a foetus and that the population of cells is self-renewing throughout live. So while these cells are not stem cells, they still manage to provide functioning macrophages throughout your whole life!
- But not all tissue macrophages stem from the time before birth. In the gut, macrophages are replaced every 2-3 weeks by monocytes from the blood. For a long time all tissue macrophages were thought to originate from monocytes in the blood. While this has been disproven for tissues such as the brain (see point 9), most tissues still see an influx of monocytes into the tissue during infection. Monocytes differentiate into macrophages to help kill the pathogens. Interestingly, differentiated monocytes cannot be distinguished from resident tissue-macrophages. So seeing a macrophage in the tissue gives you little idea where the cell originated! While this is a very interesting fact showing that the tissue-specific differences in macrophages stem from cues within the tissue, it’s also frustrating when trying to study macrophage development!
So I guess I convinced you that macrophages are awesome! Don’t agree or have 10 reasons why your favourite cells are better? Write us a guest post about it.