New research will explain extreme lung viral attacks and lead to potential COVID-1919 therapies.


Immune cells in the lungs can help make a viral infection worse in certain instances.

Researchers at the Karolinska Institutet in Sweden have identified in a new study how various types of immune cells, called macrophages, form in the lungs and which of them may be responsible for severe lung disease.

The research, reported in the journal Immunity, may lead to the treatment of COVID-19 and other diseases in the future.

They are exposed to viruses and bacteria from both the air and blood by the composition of the lungs. Macrophages are immune cells that protect the lungs from such attacks, amongst other things.

Lung macrophages, however, may also lead to severe lung diseases such as chronic obstructive pulmonary disease (COPD) and COVID-19 in some circumstances.

To date, only to a small degree has the evolution of human lung macrophages been studied.

Macrophages, which are classified into several major genetic groups, may have various origins and grow from white blood cells, monocytes, among others.

In humans, two of these are “classical” monocytes of CD14+ and “non-classical” monocytes of CD16+.

Researchers used a model to research the growth of lung macrophages directly in a living lung in a new study at Karolinska Institutet.

To discover how blood monocytes became human lung macrophages, this was combined with a tool for researching gene activity in individual cells, RNA sequencing.

We have shown in our research that typical monocytes migrate into the airways and lung tissue and are transformed into macrophages that protect the health and function of the lungs.

We have also described a special form of monocyte between a blood monocyte and an airway macrophage, HLA-DRhi, which is an intermediate immune cell.

Tim Willinger, associate professor at the Department of Medicine, Huddinge, Karolinska Institutet, who led the research, says these HLA-DRhi monocytes can leave the bloodstream and migrate into lung tissue.

On the other hand, in the many blood vessels in the lungs, the non-classical monocytes grow into macrophages and do not move into lung tissue.

“A variety of severe lung diseases are likely to be associated with some macrophages in the lungs.

For example, monocytes in the lungs grow into macrophages in respiratory infections that combat viruses and bacteria.

But a certain form of macrophage may also lead to extreme inflammation and infection,’ says Elza Evren, a doctoral student on the research team of Tim Willinger, the first author of the analysis.

Protective, anti-inflammatory macrophages are replaced with pro-inflammatory lung macrophages derived from blood monocytes during infection with the novel SARS-COV-2 coronavirus that triggers COVID-19, according to the researchers.

“The presence of these blood monocyte-derived macrophages has been shown in other studies to correlate with how severely a person becomes ill with COVID-19 and how extensive the damage to the lungs is,” he said. There are also less HLA-DRhi monocytes in the blood in patients with extreme COVID-19, possibly because they move from the blood to the lungs. Our findings indicate that potential therapies should concentrate on inflammatory macrophages and monocytes to minimize lung injury and mortality in extreme COVID-19, given their important role in rapid inflammatory responses,’ said Tim Willinger.

By Elza Evren, Emma Ringqvist, Kumar Parijat Tripathi, Natalie Sleiers, Ines Co Rives, Arlisa Alisjahbana, Yu Gao, Dhifaf Sarhan, Tor Halle, Chiara Sorini, Rico Lepzien, Nicole Marquardt, Jakob Michaelsson, Anna Smed-Sorensen, Johan Botling, Mikael C. Reference: ‘Distinct developmental pathways from blood monocytes produce human lung macrophage diversity’

Immunity.DOI: 10.1016/j.immuni.2020.12.003 I. Karlsson, Eduardo J. Villablanca, and Tim Willinger, Dec. 30, 2020.
The research is sponsored by the Swedish Research Council, the Karolinska Institutet, the Swedish Heart Lung Foundation, the Centre for Creative Medicine (CIMED)/Stockholm Area and the Swedish Cancer Foundation.

There are no conflicts of interest reported.


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