Research shows our body clock controls the inflammatory process so our cells are active and then inactive at different times.
One of the main jobs of our immune cells is to sense when an infection has occurred and react in such a way as to contain and eliminate that infection. Another lesser-known fact is that our immune cells also sense when a damage occurs to the body. That is why these immune cells – which, together, make up our immune system – are often referred to as our 'defence system'.
One of the key immune cells that does this is called the macrophage. These macrophages live in every organ or tissue and work together by constantly patrolling the body, protecting it from harmful forces. They defend us by inducing a process called inflammation. Think of what happens if you get a bee sting: your immune cells sense the venom which the bee just injected into you, and you experience redness, swelling, heat, pain and loss of function. These are the cardinal signs of inflammation. All of these things are done to get more troops of immune cells and fluid to the site where the venom is, to try and contain it and then clean up the mess afterwards.
A key question that long puzzled immunologists was how do our immune cells actually detect the presence of foreign invaders such as that nasty bee venom? What signals do they send out to the rest of the body to alert the rest of the immune cell troops to come and fight the battle?
A key part of this puzzle was solved back in the early 2000s, when these large protein complexes – called inflammasomes – were discovered. These inflammasomes, when assembled inside the cell, almost resemble a large smoke detector. Indeed, that is what they do: they are detectors for anything that looks bad or unusual, such as a bee sting.
The macrophage can sense the bee sting by forming one of its inflammasomes and, once that happens, the inflammasome starts the process of inflammation. How the inflammasome does this within the macrophage is through punching holes in the wall of itself, and all the contents of the cell spills out. It’s like turning a cell inside out. Think of having a sock filled with marbles: when the inflammasome is formed, it will empty out all those marbles on the floor.
The circadian clock
All this content from the cell is like sending up multiple flares in the sky to the rest of the immune cells that live throughout the body. They all see the flares and respond appropriately to start the inflammatory process. However, one of the questions that we are working on is whether macrophages can perform this process of inflammasome activation and turning inside out consistently throughout the 24-hour day, or whether there times when they do this really well, and other times when they take a break.
The reason we were interested to know this is because we are immunologists (we study the immune system) and clock biologists (we study the 24-hour body clock). If you're not familiar with the body clock – also known as the circadian clock – it’s based on the fact that every cell in our body has the capacity to tell the time of day. Cells just like us are more active at certain time of the day, and then take a rest at other times of the day.
Our body clock is the reason we feel sleepy at night, and active and hungry during the day. Research has shown that our body clock controls lots of processes, including the inflammatory process, but we didn’t know how the body clock was controlling the inflammatory process and whether macrophages were involved.
Morning macrophages
This unanswered question really bothered Dr James O'Siorain who was a graduate student in our lab at the time. He took macrophages in a dish, and through a couple of tricks, we were able to make the macrophage think it was either time to get up (morning), or time to go to sleep (evening).
He found that when macrophages think it’s time to get up, they can assemble their smoke detector (that is the inflammasome) much quicker and the smoke detector alarm is much louder when macrophages have to do this before it’s time to go to sleep. Because of this, morning macrophages empty out more of their contents, which causes the flares that are sent out to the rest of the body to be much brighter than when macrophages do this in the evening.
It makes sense that macrophages are responding like this according to whether its morning or evening, because you’re more likely to get a bee sting during the day, than during the night. James has been able to show that the reason for this is through our macrophage clock controlling inflammasomes.
What might be the implications for this? Well, sometimes our inflammasomes can over-defend for us and cause some inflammatory diseases like arthritis. These conditions can have worse symptoms in the morning, and this might be the reason why. We now have new medicines which may be able to be used for arthritis, and it could be that they will work better if given in the early morning at the time when macrophage inflammasomes are more active.
This article originally appeared on RTÉ Brainstorm.
Dr Annie Curtis is Associate Professor in the School of Pharmacy and Biomolecular Sciences at RCSI.
RCSI is committed to achieving a better and more sustainable future through the UN Sustainable Development Goals.
