Explaining Severe Virus Attacks on the Lungs

A recent study conducted at the at Karolinska Institutet in Sweden and published in the journal Immunity, discusses how macrophages, which are a type of immune cell, develop in the lungs and how some of them may be behind severe lung diseases. These immune cells have also been known to contribute to the worsening of a virus attack, but there has not been much research into how the human lungs develop them.

Due to the nature of the structure of the lungs, they are exposed to bacteria and viruses from the blood as well as the air. Macrophages are meant to protect the lungs from these attacks, but have also been observed under the right conditions to contribute to severe lung disease, including the chronic obstructive pulmonary disease (COPD) seen in patients with the coronavirus disease 2019 (COVID-19).

Investigators employed a model to allow them to study the development of these immune cells directly in a living lung. They also combined the model with a method called RNA sequencing that is used to study gene activity in individual cells.

The findings showed how white blood cells develop into monocytes and then become macrophages. There are 2 types of these monocytes, called classical and non-classical, and the investigators found that the non-classical monocytes that develop into macrophages do not migrate into the lung tissue.

"Certain macrophages in the lungs probably have a connection to a number of severe lung diseases. In respiratory infections, for example, monocytes in the lungs develop into macrophages, which combat viruses and bacteria,” Elza Evren, first author on the study said. “But a certain type of macrophage may also contribute to severe inflammation and infections."

The classical monocytes do migrate into the tissue, and from there are converted into macrophages that protect the health and functioning of the lungs. The investigators believe that when someone is infected with COVID-19, the protective anti-inflammatory macrophages are replaced by ones that are pro-inflammatory.

"The existence of these blood monocyte-derived macrophages has been shown in other studies to correlate with how severely ill a person becomes in COVID-19 and how extensive the damage to the lungs is. Patients with severe COVID-19 also have fewer HLA-DRhi monocytes in their blood, probably because they move away from the blood into the lungs,” Tim Willinger, the leader of the study said. “Given their important role in rapid inflammatory responses, our results indicate that future treatments should focus on inflammatory macrophages and monocytes to reduce lung damage and mortality from severe COVID-19."