When the sky becomes orange and hazy from wildfire smoke, modern humans are at greater risk than our earlier ancestors would have been.This is because mutations that occurred tens of thousands of years ago made humans exquisitely sensitive to some types of air pollution.Wildfire smoke includes two dangerous components: volatile chemicals, which include the things you can smell, and small particles, which you can’t. Both these components cause a lot of inflammation when we breathe them in and can trigger asthma attacks, and exacerbate chronic obstructive pulmonary disease (COPD) and heart attacks.We don’t have any immune defences to stop the volatile chemicals, but we do have a few layers of protection from the small particles. Some of these particles get trapped in the mucus that lines our nose, mouth and lungs and are cleared out as the mucus moves up and out of our lungs and is swallowed. (Count how many times you swallow while you read this article — you probably do it so automatically you aren’t aware of just how often you are helping clear the gunk out of your lungs). Macrophages and the scourge of tuberculosisParticles that aren’t cleared out by the mucus are generally eaten up by immune cells called macrophages. Macrophages are voracious eaters (their name means “big eater”) of things that are about the size, shape and electrostatic charge of bacteria. Unfortunately, an evolutionary quirk means that macrophages found in humans are less good at eating the particles found in air pollution and wildfire smoke than the macrophages found in other animals.The size of particle that causes us the most grief is about the same size as a bacterium (about 2.5 microns). One particular type of bacteria called Mycobacterium tuberculosis is a particular problem for our macrophages. M. tuberculosis causes tuberculosis, or TB, and has been a scourge of humanity since even before we were humans. Most bacteria do everything they can to stay away from macrophages because once they are eaten they are destroyed, but M. tuberculosis can’t survive unless it’s inside a macrophage. Once it gets into a macrophage, there’s a macrophage-pathogen quick draw and if the macrophage doesn’t win and kill it immediately, M. tuberculosis will go on to cause an infection. TB is treatable, but it still kills over a million people each year. Sometimes it will make its host get sick and die right away, sometimes it will be a long and protracted fight between the immune system and TB until the host wastes away, and sometimes it will lie latent and bide its time until the host gets old or its immune system gets distracted fighting other things and lets its guard down.Whatever path it takes, it is bad news for humans.Mutations and antimicrobial defencesTo protect ourselves, we’ve developed mutations that made our macrophages slow down the process of eating M. tuberculosis, giving the macrophage more time to alert their antibacterial defences and hopefully win the quick draw. This mutation was so useful and important that it became widespread in modern humans. Primates don’t have it and even our close cousins the Neanderthals or Denisovans don’t have it. Unfortunately, this mutation means that our macrophages are also less good at ingesting small bacteria-sized pieces of dust. When macrophages can’t do their job, these particles cause dangerous lung inflammation. This evolutionary quirk explains why humans are uniquely sensitive to particulate air pollution. Wildfires aren’t the only source of these small particles, though. They are found in industrial air pollution, busy urban centres and in dusty construction sites. Our evolutionary susceptibility to dust means that it’s important to wear a mask when you’re in an unventilated area making a lot of dust, like during a home construction project or if you are going outdoors when the air quality is poor. It also explains why there are far more hospitalizations for heart attacks and lung conditions during wildfire season and in highly polluted areas. Air pollution and healthOur susceptibility to air pollution doesn’t just have short-term health consequences that go away when the air clears up; there are also many very serious long-term health effects. People who are exposed to particulate air pollution have an increased risk of many health conditions that have inflammation at the root, like dementia. Particulate air pollution is also associated with poor pregnancy outcomes, and children who were exposed to a lot of pollution in the womb have lower measures on tests of intelligence and school performance. There are many reasons to care about climate change. The increase in wildfires and this quirk in our evolution, which impacts our short-term and long-term health, is definitely one of them.Dawn ME Bowdish receives funding from Natural Sciences and Engineering Research Council and is a member of the Board of Directors of the Lung Health Foundation.