Researchers at the University of Liège (Belgium) have discovered a new population of macrophages, important innate immune cells that populate the lungs after injury caused by respiratory viruses. These macrophages are essential for the repair of pulmonary alveoli. This groundbreaking discovery promises to revolutionize our understanding of the post-infectious immune response and opens the door to new regenerative therapies.
Respiratory viruses, which usually cause mild illness, can have more serious consequences, as demonstrated during the Covid-19 pandemic, including severe cases requiring hospitalisation and the chronic after-effects of “long Covid”. These conditions often result in the destruction of large areas of the lungs, particularly the alveoli responsible for gas exchange. Ineffective repair of these structures can lead to acute respiratory distress syndrome (ARDS) or a permanent reduction in the lungs’ ability to oxygenate the blood, leading to chronic fatigue and exercise intolerance.
While the role of macrophages during the acute phase of respiratory viral infections is well known, their function in the post-inflammatory period has been little explored. A study by the GIGA Institute of the University of Liège reveals that atypical macrophages, characterized by specific markers and transiently recruited during the early recovery phase, play a beneficial role in the regeneration of pulmonary alveoli.
The study, led by Dr Coraline Radermecker and Prof Thomas Marichal of the Laboratory of Immunophysiology, was conducted by Dr Cecilia Ruscitti and benefited from ULiège’s advanced technological platforms, including flow cytometry, fluorescence microscopy and single-cell RNA sequencing. “Our findings provide a new and crucial mechanism for alveolar repair by these atypical macrophages,” explains Coraline Radermecker. “We have detailed their characteristics, origin, location in the damaged lung, the signals they need to function and their role in tissue regeneration, acting specifically on type 2 alveolar epithelial cells, the progenitors of alveolar cells.” These macrophages had been overlooked by the scientific community because they express a marker previously thought to be specific to another population of immune cells, neutrophils, and because they only appear briefly during the repair phase before disappearing.
“Our study highlights the reparative role of these macrophages, contradicting the prevailing idea that macrophages are pathogenic after respiratory viral infections,” adds Thomas Marichal. “By targeting the amplification of these macrophages or stimulating their reparative functions, we could develop therapies to improve alveolar regeneration and reduce complications of severe respiratory infections and acute respiratory distress syndrome.”
To illustrate, consider the lungs as a garden damaged by a storm (viral infection). These newly discovered macrophages act as specialized gardeners, clearing away debris and planting new seeds, allowing the garden to grow back and regain its vitality.
This scientific breakthrough underlines the importance of research at the University of Liège and opens up new avenues for the treatment of respiratory diseases.