Making the switch in immune cells to fight TB

Research lives: Dr Laura Gleeson, specialist registrar in respiratory medicine

Dr Laura Gleeson: “In the lab, you are working towards long-term goals, slowly testing hypotheses and accumulating evidence to answer questions that have never been asked before.”

Dr Laura Gleeson: “In the lab, you are working towards long-term goals, slowly testing hypotheses and accumulating evidence to answer questions that have never been asked before.”

 

You are a medical doctor, how did you become interested in research?

“I had done my medical degree and my basic medical training at Trinity College Dublin and St James’s Hospital, and when it came time to choose a specialist area, I wanted a bit of time to think about it. I took a post as clinical lecturer at St James’s Hospital, and while I was there I became really interested in the research that Prof Joe Keane was doing on TB, so with funding from the Health Research Board, I undertook a PhD in his lab.

You have been researching how our bodies fight TB. What have you been looking at?

I’m interested in cells in the immune system called macrophages. We know that when macrophages are stimulated they change their metabolism and burn fuel in a different way, known as the glycolytic shift. This change in metabolism has been linked to inflammation and sepsis. But I was interested in whether macrophages in the lungs did this when they were infected, and whether it might actually be helpful for fighting an infection like TB.

How do you research something like that?

Patients who were undergoing bronchial procedures very kindly allowed me to take washings from their lungs, and from those samples I was able to grow macrophages in the lab. Then I looked at what the macrophages growing in the lab did when I confronted them with the TB bacteria.

What did you find?

I saw that after infection, macrophages did undergo this glycolytic shift, and that this made them better at attacking and clearing the TB bacteria – showing for the first time that the glycolytic shift is beneficial and even vital in allowing us to fight infections better. Interestingly though, when I looked at macrophages isolated from smokers, I saw the cells had a lower rate of activity generally, and they couldn’t make that fuel-burning shift to fight the bugs. Essentially, smokers’ immune cells are bio-energetically exhausted, and this may explain why smokers are more susceptible to TB infection.

How might the findings ultimately help patients?

I identified certain drugs that can encourage macrophages to switch into this fuel-burning mode, ultimately ramping up the defences against bacteria. This kind of approach could help to support people as they try to mount an immune response to TB, improving patient outcomes.

You have experienced life as a clinician and life as a lab researcher, are they very different?

Yes, very different! As a doctor in a hospital, you are working closely with patients, figuring out what they need and how to help each individual. Every day is different and brings unexpected challenges and experiences.

In the lab, you are working towards long-term goals, slowly testing hypotheses and accumulating evidence to answer questions that have never been asked before. You have the freedom to experiment and follow your ideas and curiosities. I love both clinical practice and research, and would love to combine both in my career going forward.

What do you do to take a break from work?

I love travelling, and whenever I have time off I try to visit somewhere new. A break always feels twice as long when you experience something completely different and new, and you come back feeling refreshed and energised.”