How the body repairs lung tissue after viral pneumonia

An international research team from the DZL, led by Lung Research of Giessen, has discovered a new repair mechanism with therapeutic potential. The work has now been published in "Nature Communications".

How does the body repair damage to the lung tissue after a viral pneumonia and how can these processes be influenced therapeutically? An international research team led by Giessen lung and infection researcher Prof. Dr. Susanne Herold, Professor of Internal Medicine, Infectiology and Experimental Pneumology at Justus Liebig University Giessen (JLU), is investigating these questions. Infections with respiratory viruses such as influenza viruses, the viruses that cause influenza, RS viruses or coronaviruses can trigger viral pneumonia, which in the worst case can lead to lung failure. The scientists have now been able to identify a protein that mitigates the lung damage caused by influenza viruses and could have therapeutic potential. The results have been published in the journal "Nature Communications".

Severe pneumonia is associated with a rapid decline in gas exchange in the lungs, so that rapid regeneration of the damaged lung tissue is necessary. Macrophages, also known as phagocytes, play an important role in the repair of lung damage caused by inflammation. They are an essential component in the immune defense processes and ensure, among other things, that pathogens are broken down in the body. A distinction is made between site-independent macrophages, which are transported to the site of action via the blood as required, and "sedentary" macrophages, which are produced by the immune system. Tissue-resident alveolar macrophages are long-lived cells in the alveoli, where the gas exchange between blood and air takes place. Here they ensure stable conditions in the lung tissue (tissue homeostasis) and are involved in the direct defense against pathogens. Several studies have shown that alveolar macrophages are decimated during viral pneumonia and are gradually replaced by mobile macrophages originating from the bone marrow during the course of the infection. These transform into alveolar macrophages in the inflamed lung.

The research team has discovered that during the transformation process of mobile macrophages into alveolar macrophages, the protein Plet1 is produced to a high degree. Plet1 plays an important role in lung repair by inducing the proliferation of alveolar epithelial cells - specialized cells that line the alveoli - and the resealing of this cell layer barrier. These positive effects could also be induced externally: The administration of Plet1 mitigated viral lung damage in the preclinical model and led to a significantly faster recovery after a severe infection, which is otherwise fatal. "For the first time, we have identified a factor that directly mediates the repair of the damaged lung. This finding underlines the therapeutic potential of Plet1 to combat severe lung damage in viral pneumonia, and possibly also in other forms of acute or chronic lung failure," says DZL scientist Prof. Herold.

Scientists from various Giessen infection and lung research institutions - German Center for Lung Research (DZL), University Hospital Giessen and Marburg (UKGM) at the Giessen site, Universities of Giessen and Marburg Lung Center (UGMLC) - were involved in the study, German Center for Infection Research (DZIF), Institute of Lung Health (ILH), Cardiopulmonary Institute (CPI) Cluster of Excellence, the Universities of Heidelberg and Bonn, the Max Planck Institute for Heart and Lung Research in Bad Nauheim and the Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA) in Buenos Aires (Argentina).

Original publication: Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia. Pervizaj-Oruqaj, L., Selvakumar, B., Ferrero, M.R. et al. Nat Commun 15, 87 (2024).

Source: DZL