Study Sheds Light On New Lung Cells

This story is part of a series exploring human anatomy and physiology complexities. Each story in this collection showcases discoveries reshaping our understanding of the body’s inner workings, potentially changing the way we teach and learn about it in the future.

This new series of articles on human anatomy is a testament to the never-ending quest for knowledge that has propelled the field of medicine forward throughout history. The importance of anatomical discovery over time cannot be overstated—the key has unlocked the mysteries of life and the essence of our being. 

Traditionally, our knowledge of the lung’s anatomy and physiology has been extensive yet incomplete. We’ve known about the bronchi, alveoli, and the pulmonic circulation system and how they facilitate the vital exchange of oxygen and carbon dioxide. We’ve recognized that the body’s immune system—with its white blood cells and antibodies—plays a critical part in defending against respiratory infections like the flu.

However, until recently, a particular cohort of cells stationed at the forefront of our lungs’ defense, acting as stealthy guardians against the onslaught of infectious agents like the influenza virus, remained hidden. A recent study published in Proceedings of the National Academy of Sciences sheds light on these special lung immune cells. 


What We Know About the Lung Cavity and Immune Cells


The pleural cavity, home to our newly discovered macrophages, has remained somewhat enigmatic, its precise influence on immune responses to infection largely uncharted until now.


The pleural cavity is a space surrounding the lungs that contains pleural fluid and immune cells, including macrophages. Macrophages are immune cells that play a critical role in the immune response to infection. They are known to be involved in the resolution and progression of influenza. Still, their specific role in these outcomes is not fully understood. 


The study by Stumpff and colleagues delves into the role of these pleural macrophages. It sheds light on how macrophages play a part in the resolution and progression of influenza. Yet, the factors driving these outcomes remain elusive. By analyzing lung gene expression data from mouse models with varying disease severity, the researchers predicted immune cell variances linked to different disease results. 


In-Depth Look at the Lung Study


The study used lung gene expression data from mouse models of mild and severe influenza to predict immune cell differences associated with different disease outcomes. They used a Digital Cell Quantifier algorithm to identify immune cell subsets correlated with mild or severe virus infection outcomes. They identified a unique lung macrophage population that transcriptionally resembled small serosal cavity macrophages and whose presence correlated with mild disease. 


The researchers established a mouse model of the disease to confirm their findings. They showed that pleural macrophages migrate from the pleural cavity to the lung after infection. They found that the depletion of pleural macrophages increased morbidity and pulmonary inflammation. There were increased proinflammatory cytokines in the pleural cavity and an influx of neutrophils within the lung. 


However, this study has limitations. It was only conducted in mouse models, and further research is needed to determine if these findings hold in humans. Additionally, the study only looked at the impact of these cells on one strain of influenza virus, and it is unclear if the results apply to other viruses.


Implications of the Study and What It Can Lead to in the Future


The study has significant implications for understanding the immune response in the lungs and developing new treatments and vaccines. By understanding the role of pleural macrophages in influenza and respiratory disease outcomes, researchers may be able to create new therapies that target these cells. Additionally, the study may lead to the development of new vaccines that stimulate the migration of pleural macrophages to the lungs.


The discovery of pleural macrophages translocating to the lung during infection to promote improved outcomes is a significant step forward in understanding the immune response. While the study has limitations, the findings have important implications for developing new treatments and vaccines. 

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© William A. Haseltine, PhD. All Rights Reserved.