Why are we more prone to infection as we get older?

Wezi, a Clinical Research Fellow at Newcastle University, had to pause his PhD research earlier this year due to the COVID-19 pandemic, as he returned to full-time clinical practice as a respiratory physician at the Royal Victoria Infirmary in Newcastle.

He tells us about the experience of treating COVID-19 patients and explains how his PhD research could lead to better treatments for age-related diseases, reducing the reliance on antibiotics and allowing people to live longer, healthier lives.

Wezi’s PhD project focuses on understanding the role ageing has on inflammation and lung infections, such as bacterial pneumonia.

As we get older, we become more susceptible to lung infections like bacterial pneumonia. This susceptibility means that antibiotics may need to be used more frequently in older patients, which can lead to antimicrobial resistance and infections that become increasingly difficult to treat.

Part of this increased susceptibility to infections as we grow old is down to a change in the process of inflammation, which is the initial immune response to invading bacteria. As we age, inflammation is slower to subside once an infection is cleared and may even turn into persistent low-level inflammation, and this can cause collateral damage that makes infection more likely in future.

Lung immune cells under the microscope

The immune cells in the lungs that regulate the immune response to infection are called ‘alveolar macrophages’. By sampling these cells from the lungs of healthy volunteers, Wezi’s research looks at what changes in their behaviour as we age to stop them from turning off inflammation after an infection has settled.

Wezi recruited his first study volunteer in March, just a lockdown began. “As a respiratory doctor by trade, I was already keeping an eye on reports coming out of China. When the NHS called for help in March, I volunteered to join the COVID-19 response at Royal Victoria Infirmary,” says Wezi.

“Until May this year, I was treating people with shortness of breath, fever and coughs, many of whom ended up having positive COVID-19 tests. As it turned out, there was a strange serendipity to this, as I’ve ended up using some of the things I learned from treating COVID-19 patients in my own PhD research.”

Now back in the lab, Wezi is examining what changes in the immune system as people get older to make them more prone to infection. “I’m interested in why someone with pneumonia in their 70s is less likely to get better from that infection, compared to someone in their 20s,” says Wezi. “By looking at immune cell samples from the lung airways, we can examine how the cells’ behaviour changes as people get older. How do these initial immune defences become weaker, when faced with an infection, and what causes that molecular switch?

“With targeted treatments for age-related diseases, we may be able to boost the immune response in older people. This would make them less likely to have severe infections, which would reduce reliance on antibiotics and, ultimately, reduce the wider spread of antimicrobial resistance.”

Wezi recently won the prize for the best oral presentation when he presented his research to colleagues and members of the public at a local National Institute for Health Research (NIHR) Trainee Showcase.