A common genetic variant can weaken the lungs' defences against bacteria and increase the risk of pneumonia. This is shown by a new study led by researchers at Lund University in Sweden. The researchers have also discovered a previously unknown mechanism by which the immune system in the airways detects and combats bacteria.
Pneumonia is a common and sometimes serious infection that affects 20,000-30,000 people in Sweden every year.
Well-known risk factors include advanced age, smoking and underlying medical conditions. In a new study, researchers at Lund University and Skåne University Hospital have shown that genetic differences in the innate immune system can also influence the risk of developing the condition.
"We investigated how a common genetic variant - carried by roughly one in seven Europeans - affects the immune receptor Dectin-1. The receptor is found on cells in lung tissue, where it recognises foreign substances and helps the body to respond to them," says Kristian Riesbeck, professor of clinical bacteriology at Lund University and senior consultant in clinical microbiology at Skåne University Hospital.
Dectin-1 has previously been associated mainly with protection against fungal infections, but the study shows that the receptor also plays a significant role in defending the airways against bacteria. The analysis covered just over 28,000 participants in the Malmö Diet and Cancer Study. The participants were followed for an average of more than 17 years, during which time around 5,500 cases of pneumonia were recorded.
"The genetic variant causes the receptor to function less effectively. Carriers had an approximately 12 per cent higher risk of developing pneumonia, even when we took into account smoking, body weight and medical conditions that affect the immune system,"continues Kristian Riesbeck.
The researchers were surprised that a single, relatively common genetic variant could have such a significant impact. As this variant is common, it may affect many people, even though the increased risk for each individual is moderate. The increased risk persisted when the analysis was restricted to bacterial pneumonia, which strengthens the link to the lungs' defences against bacteria.
To understand the mechanism behind the increased risk, the researchers also carried out experiments on mice. When the immune system's receptor was absent or functioned less effectively, the mice found it more difficult to clear two common bacteria that can cause respiratory tract infections: pneumococci and Haemophilus. The less effectively the receptor worked, the less successfully the body was able to get rid of the bacteria.
"We also discovered that the receptor helps the immune system to recognise bacteria and trigger the body's defences. If the receptor does not function as it should, we therefore also become less effective at fighting off bacteria," says Oskar Thofte, a postdoc at Lund University.
The discovery reveals a previously unknown way in which the lungs' immune system detects bacteria. In the long term, the findings may contribute to a better understanding of why some people are more susceptible to infections than others.
"In my 30 years as a researcher, this is one of the studies I am most proud of. I began researching Haemophilus as far back as 1999, and my long experience of the bacterium has been crucial to this work. But it is only with today's techniques, including whole-genome sequencing, that we have been able to analyse the participants' genetic background and achieve these results," concludes Kristian Riesbeck.
