„You eat the cookies. I clean up the rest.“
Hi, I’m Marco, a macrophage – a professional “eater cell” and clean-up crew of the immune system. While you’re busy digesting cinnamon stars, roast goose, and chocolate in December, I’m doing exactly what my name promises down in the tissue: I eat.
I’m part of the innate immune system, the fast, non-specific line of defense. Whenever something goes wrong in the body as an injury, an infection, or cell damage, I’m usually one of the first on the scene.
What defines me:
My breakfast isn’t exactly Instagram-worthy, but it’s highly functional.
On my surface I carry different recognition receptors, for example for typical structures on bacteria or viruses, or for signals from damaged body cells. When I detect such a signal, I wrap my cell membrane around the target and take it up as a whole. That’s called phagocytosis.
Inside, this “food vesicle” fuses with lysosomes, which are full of digestive enzymes and aggressive molecules. There the prey is chopped into tiny fragments – rendered harmless and partly recycled.
You have a vacuum cleaner for crumbs on the carpet; your body has me for microscopic crumbs in the tissue.
When I run into real danger, for example bacteria or viral structures, I switch into an M1-like state, my attack version.
Then, among other things:
In this mode I’m security, fire brigade, and special forces all rolled into one cell. In the short term that’s extremely useful, but in the long run it’s risky, because too much inflammation damages the tissue.
When the acute danger is over, or when the main issue is tissue damage, I switch into an M2-like state – my healer version.
Then I behave differently:
You could say: in M1 mode I stir things up, in M2 mode I restore order. In reality there are lots of intermediate states, but this picture helps to grasp the basic idea.
I, Marco, am a “classic” tissue macrophage. But I have specialized relatives all over the body:
Our surroundings shape us: the tissue determines which genes we switch on, which surface molecules we carry, and which tasks are top priority. But wherever we are, eating and regulating are always at the core of our job.
I’m not just an eater; I’m also an information service for the adaptive immune system, the “smart” part with memory.
Some of the fragments produced from what I’ve eaten are loaded onto special serving plates on my surface, the MHC class II molecules. T helper cells recognize this combination of antigen and MHC and become activated.
This has several consequences:
In pictures: I’m basically giving the immune system a PowerPoint talk: “This is the intruder. Please remember and attack precisely.”
In December, energy intake is high for many people and movement is rather low. In fatty tissue, especially in obesity, my environment changes as well.
More macrophages can move into the fat tissue and linger in a chronically pro-inflammatory state. Then my kind produces inflammatory messengers over a long period of time without any classic infection being present.
That’s called low-grade chronic inflammation and it plays a role in conditions such as insulin resistance, type 2 diabetes, atherosclerosis, and certain liver and joint diseases.
If there’s a permanent Christmas buffet on the outside, my delicate balance between M1 and M2 inside can tip over … and that can cause trouble in the long run.
In tumours I often show up as a tumour-associated macrophage. My role there is pretty ambiguous.
In a more M1-like state I can attack tumour cells, boost signals for their destruction, and encourage other immune cells to join in. In a more M2-like profile, however, I can support processes that benefit the tumour, such as blood vessel formation, tissue remodelling, and dampening of immune responses.
That’s why cancer research is trying hard to reprogram me in the tumour environment: away from tumour-supporting functions and towards anti-tumour activity.
I’m also frequently involved in chronic inflammation of joints, gut, brain, or vessels when an inflammatory reaction isn’t properly switched off and turns into a long-term state.
While you’re sitting on the sofa in the evening with mulled wine and cookies, I’m still active, often in the background.
Some of us are constantly generated from monocytes in the blood that migrate into tissues and develop into macrophages there. Other macrophages have been in the tissue since embryonic life and renew themselves locally. Together we continuously watch over the tissues, help decide whether a reaction escalates or stays controlled, and contribute to cleaning, repair, and stability of the body’s inner environment.
