Researchers at the University of Illinois at Chicago have discovered that immune cells in the lungs known as alveolar macrophages can be “trained” to memorize previously encountered pathogens. This learning enhances their ability to clear cellular debris from the body and reduce inflammation during infections. The findings suggest that these immune cells possess a form of “trained immunity,” which could have significant implications for the treatment of various diseases. The study was published in the Journal of Experimental Medicine
Alveolar macrophages are responsible for clearing debris from the lungs and protecting them from pathogens and inhaled environmental particles. They play a critical role in regulating inflammation and organizing the lung’s immune response. Recent studies have shown that these cells can retain a memory of repeated exposure to pathogens, leading to an improved immune response.
To study the trained immunity of alveolar macrophages, researchers infected mice with an inhaled bacterial toxin called lipopolysaccharide (LPS). After the first exposure to LPS, alveolar macrophages helped reduce the severity of inflammation when they were exposed again a week later. These trained cells produced significantly higher levels of the anti-inflammatory cytokine interleukin-10 (IL-10) without increasing levels of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha).
Toxin memory persisted even when the second exposure occurred one month after the first exposure. The trained alveolar macrophages became very efficient at removing pro-inflammatory cellular debris that accumulated after infection. This is very important because persisting debris can trigger prolonged immune system responses and increase inflammation.
In another experiment, researchers infected mice with the bacterium Pseudomonas aeruginosa, which can cause pneumonia in humans. Mice that were “trained” with this bacterium had significantly higher levels of alveolar macrophages and fewer neutrophils, which are the first immune cells recruited to foci of inflammation. This suggests that the trained cells helped to reduce the degree of inflammatory damage.
The unique characteristics of alveolar macrophages make them particularly promising for therapeutic applications. These cells are present in the lungs from childhood through adulthood and are capable of regenerating from surviving cells. In addition, they transmit epigenetic information to their progeny, allowing new macrophages to retain the memory of previous infections.
The researchers believe that trained alveolar macrophages could potentially reduce the risk of acute lung damage caused by various diseases. In addition to treating lung disease, these cells could be valuable in cell-based therapies that limit inflammatory damage in autoimmune diseases such as type 1 diabetes or in organ transplantation.
The study opens new avenues for further investigation of macrophages in other organs. In the future, it may be possible to investigate whether macrophages in other organs can also learn from initial infections, potentially leading to advances in the treatment of various diseases.