The Nose Knows When It’s Cold—And It May Get You Sick

IRA FLATOW: This is Science Friday. I’m Ira Flatow. In case you haven’t noticed– and who hasn’t– we are now in the cold and flu season. It’s the time of the year when it’s cold outside, and you’re more likely to see people sneezing and coughing– of course, the classic hallmarks of a respiratory infection. What’s interesting about this time of the year is that it’s usually assumed that the reason so many more people get sick is because we spend more time together locked up indoors.

But new research out of Harvard Medical School and Northeastern University finds that there’s a biological reason for this seasonal variation. And it all goes back to your nose. Joining me now to talk about this breakthrough is my guest, Dr. Benjamin Bleier, associate professor at Mass Eye and Ear and senior author of this study. He’s based in Boston, Massachusetts. Welcome to Science Friday.

BENJAMIN BLEIER: Hi, Ira, great to be here.

IRA FLATOW: I am so glad to hear what you have learned because my mom always told me to bundle up outside in the cold, or I’m going to get sick. But now along comes your research, and it turns out that Mom was sort of right. The cold air does have something to do with it, cold air, when it gets in through your nose. Tell us what you’ve uncovered.

BENJAMIN BLEIER: Well, yeah, it does turn out that our mothers and grandmothers were right all along, which perhaps is not surprising. But our study looked at the function of viruses as they get in to the nose and how our body fights against them. And you can kind of break our study down into two parts. The first is we actually discovered a novel, innate immune mechanism, or a way that our immune system fights off viruses as soon as they enter our nose. And then the second part of the study was to look at how that function is actually impaired when we’re exposed to cold air.

So the first part of the study asks the question, how does our nose fight and prevent viruses from infecting the cells? And what we found was a very interesting mechanism, which actually takes off on some research we had done several years prior with regards to bacteria. And essentially, what we found is that when you inhale a virus, the front of the nose is really the first part that the virus sees and impacts on those cells.

And that essentially alerts the nose that the virus is present because it binds to a receptor, which is called a toll-like receptor. Now these receptors are actually evolutionarily coded in our bodies to already recognize these viruses, even if we’ve never actually been exposed to them before. But this sets off this cascade of events within the nose that results in three very important features of the immune response.

The first is that the cells release what we like to call a swarm of extracellular vesicles. You can think of these as little bubbles that are released from the cells into the nasal mucus. And we found that when a virus is introduced to the nose, about 160% more of these little bubbles are released into the mucus. But it’s not just the number of these bubbles that changes. It’s actually the composition, how these little bubbles are packaged.

So the first thing we found is that these bubbles are actually decorated on the surface with the same receptors that the virus uses to get into our cells. But the receptors are actually increased up to 20 times. So there’s 20 times more of these receptors on the surface of these vesicles. So essentially they act as little decoys. So the virus will bind to these vesicles and get mopped up before they ever have a chance to bind to the cells. So that’s sort of the first way that these vesicles work.

The second is that on the inside of these vesicles, these bubbles, there’s a whole array of complex molecules that actually kill the viruses. Now we look specifically at a type of molecule called a microRNA, and in this case, microRNA 17, which is a microRNA, which has been previously shown to have antiviral effects. And we found that these vesicles have up to 13 times more microRNA 17 than before you were exposed to the virus. And so essentially, these vesicles bind to the virus because they act as these decoys, and then the virus is inactivated by the presence of this high concentration of microRNA.

So this is a really cool mechanism because this is essentially what we’re finding is that this is your body’s immune system leaving the body itself to go into the outside world to protect itself against the viruses before the virus can actually bind to the cell. The analogy we like to use is it’s like a hornet’s nest. So when the hornets are aware of an intruder, they swarm out of the nest to go attack the intruder before they have a chance to get into the nest itself.

IRA FLATOW: Wow, that’s cool.

BENJAMIN BLEIER: Yeah, and we thought so as well. Now that was the first part of the study. But when we were thinking about this, we know that this whole response, everything that we’re talking about, is happening really at the front of the nose. The front of the nose is the part of the body that’s most exposed to the external environment, all the bacteria and viruses and fungus in the air and other irritants. And we inhale about 10,000 liters of air a day. So you can see that the front of our nose is constantly being assaulted with this type of external irritants and, again, pathogens.

But at the same time, we realize, well, not only is it exposed to what’s in the air, but it’s also exposed to the temperature of the air itself. And so if there’s any part of the body that’s going to be sensitive to the changes in temperature in our environment, it’s going to be the front of the nose, because this is exactly the area that first is impacted by that cold air before the body has time to warm and humidify it, so that by the time it gets into our lungs, it’s actually at body temperature and at about 100% humidity. So that was what kicked off the second part of our study asking what is the effect of that cold air on the immune response.

IRA FLATOW: And the second part, you talked about what happens when it gets cold in your nose?

BENJAMIN BLEIER: Exactly. We wanted this study to really reflect what happens in live people. And so what we did was we took little, tiny temperature probes called a thermocouple. And using a small scope, we were actually able to guide this into the noses of healthy volunteers and measure the change in their nose in different places in their nose at different external temperatures. And what we found is that if you go from room temperature down to about 40 degrees, just that change in temperature externally drops the temperature in the nose about 5 degrees Celsius, or about 9 degrees Fahrenheit.

And so we then applied that same fairly modest drop in temperature to the studies that we just described about the immune response. And we found that in all three of these important effects were all impacted negatively by just this small change in temperature. So, for example, the number of these vesicles that are released dropped by about 40%.

IRA FLATOW: Wow.

BENJAMIN BLEIER: The amount of that protective microRNA dropped by about 25%. And the number of the receptors that we discussed dropped by about up to 75%. So in all of these different types of mechanisms, we have this decline in function. And what that translated to, what we found in culture, was that there was almost a doubling of the amount of virus able to replicate within the cells, again, just by this small temperature drop.

And so essentially, what this means is that when we’re exposed to cold temperature in the front of the nose, the immunity, our ability to fight off these viruses drops by about half. And so, essentially, it only takes about half as much virus to cause an infection in any individual, as we get into these colder months. And again, this was even just a drop to 40 degrees.

IRA FLATOW: That’s amazing. My question to you then is, now that we’re dealing with COVID and our noses, and we’re wearing masks, if the mask keeps your nose warmer because you’re recirculating, right, all that warm air, could that help you fight off a COVID virus, as well as a cold virus?

BENJAMIN BLEIER: Yeah, so you hit the nail right on the head there, which is now that we understand this novel response, how do we use it to our advantage to prevent infection? And I think what you described is really the most short-term actionable item that we can do. I think what we’ve shown is that we know that masks prevent us from being exposed to the virus.

But just as you said, now we believe that these masks also preserve this cushion of warm air in front of our noses and further reduce our ability to be impaired from the infection, which essentially means that all this time, masks have probably been acting in two different ways. And that probably responds to why they’re so effective with prevention of viruses.

IRA FLATOW: So what are the implications of this discovery, then, for treating upper respiratory infections?

BENJAMIN BLEIER: Well, this discovery really, as I mentioned, pertains to the innate immune response. This is the immune response that prevents us from getting the infection in the first place. This is different than the adaptive immune response, which is, for example, what happens when we get vaccinated. That’s why vaccinations take weeks to kick in for our antibodies to develop.

So what we’re talking about here is really prevention as opposed to treatment. What we’ve found is that essentially, when the body is convinced that there’s a virus present, it kicks off this entire response. So if we can develop topical sprays, for example, that mimic the presence of a virus without the actual pathogenicity or the injurious part of the virus, then we can fool the nose into thinking a virus is present and increase the amount of these protective vesicles, even without having to actually be exposed to the virus.

IRA FLATOW: Well, I want to– this is great. Great to learn. Great to have you on and tell us about it. Thank you for taking time to be with us today.

BENJAMIN BLEIER: Oh, it’s been my pleasure.

IRA FLATOW: Dr. Benjamin Bleier, associate professor at Mass Eye and Ear and senior author of this study. He’s based in Boston.

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