Nat Immunol: Revealing New Mechanisms of Increased Immunity Following Lung Infection

According to a recent study by the Francis Crick Institute, the immune system's response to respiratory infections is constantly changing, depending on the history of previous unrelated infections.

The body has two kinds of immunity to infection. Adaptive immunity provides an immune "memory" that can respond rapidly and strongly when the same disease occurs more than once. In contrast, innate immunity provides a broad and less specific first line of defense against all pathogens, and is essential for controlling infections that the body has not previously experienced.

The study, published in Nature Immunology, found that after recovery from respiratory infections, certain cells in the innate immune system of the lungs would more effectively provide additional protection against new infections over the next few weeks. Specifically, they found that mice injected with the influenza virus had a significantly lower likelihood of contracting completely different bacterial infections a month later.

This enhanced immunity is the result of a specific type of immune cell entering the lungs from the bone marrow during the initial infection, becoming pulmonary macrophages (a type of white blood cell). Once in the lungs, these cells produce cytokines—hormone-like molecules that cause inflammation and help fight pathogens.

Since these specialized macrophages are still in a more active state in the lungs after the infection has resolved, they provide an additional layer of protection over the next few weeks to prevent future infections. However, the ability of these macrophages to produce high levels of cytokines disappeared over time. This means that after a few months the resistance to infection declines and eventually returns to the level of previously uninfected animals. Researchers believe that this mechanism also applies to humans.

"Influenza is a serious disease, especially for vulnerable groups, so we are not saying that influenza infection is beneficial, but rather, this study provides us with valuable insights into how a rapidly cleared viral infection, through long-term changes in innate immune cells, continues to affect immunity in the following weeks. This may partly explain why our response to the disease is ever-changing—you can beat the disease without symptoms within a week, but it can have a serious impact in a few weeks," said Helena Aegerter, lead author and doctoral student at the Immunomodulation Laboratory at the Francis Crick Institute.

The investigators plan to further investigate how a history of infection affects the immune system, including in conditions such as asthma or chronic obstructive pulmonary disease, where the exacerbated inflammatory response explained in this study may exacerbate symptoms.

The level of protection of our immune system is not constant. This means that it is important for people to take long-term infection prevention measures in appropriate places, such as winter influenza vaccines.