Unique Lung Immune Cells Play a Vital Role in Combating COVID-19 Inflammation

A recent study has unveiled the significant role of a rare type of lung immune cell in the fight against COVID-19. These cells, known as nerve and airway-associated interstitial macrophages (NAMs), are critical for managing the body's inflammatory response during SARS-CoV-2 infection.

Conducted by researchers from NYU Langone Health, the study explored the effects of NAMs in mice infected with the virus. Scientists discovered that NAMs help control the initial immune response, preventing excessive inflammation that can lead to severe complications and death. In experiments, mice lacking these macrophages exhibited increased viral spread, greater weight loss, and heightened inflammation, ultimately leading to a 100% mortality rate. In contrast, mice with intact NAMs demonstrated limited viral proliferation and survived the infection.

Macrophages, which are large immune cells, are known for their role as the first responders to infections. They engulf and destroy invading pathogens, contributing to inflammation as a part of the immune response. The findings from this study suggest a paradigm shift in treating COVID-19, emphasizing the need to manage the immune response rather than solely enhancing it.

According to the research, NAMs are not only crucial for controlling inflammation but also depend on a protein called type 1 interferon receptor (IFNAR) to perform their functions effectively. When researchers genetically modified NAMs to eliminate their ability to produce IFNAR, a similar mortality rate was observed as in NAM-depleted mice, underscoring the importance of this receptor in regulating immune responses.

The study also included analyses of lung tissue from patients who had experienced severe COVID-19 symptoms, revealing decreased activity of NAM-related genes in those who did not survive. This correlation between mouse and human data strengthens the argument that NAMs play a similar protective role in humans.

Further elaborating on the implications of the findings, senior researcher Kamal Khanna highlighted the potential for developing new treatment strategies that leverage IFNAR signaling to enhance disease tolerance. This approach could extend beyond COVID-19 to other respiratory illnesses, such as chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis.

The ongoing research aims to deepen the understanding of NAM pathways and their interactions during SARS-CoV-2 infection, focusing on how type 1 interferon can stimulate NAM growth. The insights gained could pave the way for innovative therapies aimed at modulating the immune response in various pulmonary diseases.