Common Gene Variant Raises Pneumonia Risk

A common genetic variant can make the lungs less able to fend off bacteria, raising the risk of pneumonia, according to a new study led by researchers at Lund University. The work also uncovered a previously unknown mechanism through which the airways’ immune system detects and fights bacteria.

Pneumonia is a widespread infection, sometimes serious, that strikes an estimated 20,000 to 30,000 people in Sweden each year. Advanced age, smoking, and underlying health conditions are well-established risk factors, but the new study, from Lund University and Skåne University Hospital, shows that genetic variation in the innate immune system can also shape a person’s risk of developing the illness.

According to Kristian Riesbeck, senior author of the study published in eBioMedicine,  “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 recognizes foreign substances and helps the body to respond to them.”

Dectin-1 had previously been linked mainly to defense against fungal infections, but this study finds that the receptor also plays an important role in protecting the airways from bacteria. The researchers analyzed data from just over 28,000 participants in the Malmö Diet and Cancer Study, following them for an average of more than 17 years, during which roughly 5,500 pneumonia cases were recorded.

Riesbeck continued: “The genetic variant causes the receptor to function less effectively. Carriers had an approximately 12 percent higher risk of developing pneumonia, even when we took into account smoking, body weight and medical conditions that affect the immune system.” 

The researchers said they were surprised that a single, fairly common genetic variant could have such a notable effect; because it’s so widespread, it could affect large numbers of people even though the added risk for any one person is modest. The elevated risk held up when the analysis was narrowed to bacterial pneumonia specifically, reinforcing the link to the lungs’ bacterial defenses.

To probe the underlying mechanism, the team also ran experiments in mice. When the receptor was missing or working less effectively, the mice had more trouble clearing two bacteria that commonly cause respiratory infections, pneumococci and Haemophilus—the weaker the receptor’s function, the less successfully the bacteria were eliminated.

First author Oskar Thofte added: “We also discovered that the receptor helps the immune system to recognize bacteria and trigger the body’s defenses. If the receptor does not function as it should, we therefore also become less effective at fighting off bacteria.”

The finding points to a previously unrecognized way the lungs’ immune system senses bacteria, and could eventually help explain why some people are more prone to infections than others.