Ageing immunity

Researchers study the immune response to respiratory infections with the goal of understanding why the response deteriorates as we age. The overall goal of this work is to identify strategies to prevent this decline in immune function.

Elderly woman looks out window

It is a known fact that older people are more susceptible to respiratory infections. Each year we hear the call for older people to get their flu shots. Throughout the pandemic, older people have been consistently identified as a vulnerable population for contracting SARS-CoV-2. But why?

A team of researchers at the Doherty Institute and Monash University took us one step closer to understanding this susceptibility with a study showing how age impacts the composition of immune cells in the lung and how these changes influence the ability of the tissue to respond following exposure to respiratory infections.

Published in Clinical and Translational Medicine, the findings linked a lag in antiviral response to these viruses to an age-associated decay of a specific immune cell in the lung.

The study came about when the team were characterising immune cells as part of a previous study.

"We had set up a human lung biobank to specifically look at a particular immune cell in the lung, termed CD8+ tissue resident memory T cells, an immune cell designed to kill virus-infected cells," says University of Melbourne researcher Dr Linda Wakim, a Laboratory Head at the Doherty Institute and senior author on the paper.

We started noticing that the frequency of these cells was markedly different from sample to sample. When we looked at what seemed to be causing these differences, the standout was age. We obviously wanted to explore that more and understand what impact this deterioration had on the body's ability to combat respiratory diseases," Dr Wakim says.

The researchers took lung tissue from organ donors of various ages, infecting the tissue with either influenza virus or SARS-CoV-2 and looked at how the tissue responded to the infection.

Following infection with flu, the adult tissue, with sufficient stores of CD8+ tissue resident memory cells, produced a lot of inflammatory factors known to be able to limit virus replication. However, the tissue from donors over the age of 65, where these specific cells had begun to wane, did not result in the same rapid and robust antiviral response.

"There was a clear link between this antiviral response and the quantity of CD8+ tissue resident memory cells present," explains Dr Wakim.

"We think that this loss of the local memory T cell pool may, in part, explain the increased vulnerability of the elderly to respiratory infections."

3D render image of lungs

When they infected the tissue with SARS-CoV-2, neither younger nor older adult tissue could generate a rapid antiviral response.

The charateristic of the SARS-CoV-2 virus to not initially trigger a robust antiviral response has already been described by other studies.

The team is hopeful that a better understanding of age-associated changes that occur in the lung immune response will allow for the development of strategies that boost or preserve these immune cells and improve the capacity of older people to combat respiratory infections.

In fact, they are currently working on a vaccine candidate that would do just that.

"They work wonderfully in mice -- we just don't know yet if that will translate into humans."