They discover why the elderly are more vulnerable to flu and other respiratory infections |  Universal News

They discover why the elderly are more vulnerable to flu and other respiratory infections | Universal News

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Older people often have a worse prognosis when they have viral infections in the lungs, such as the flu or COVID-19. Among the different factors that complicate the evolution of these infectious diseases is an uncontrolled inflammatory response, which harms patients by causing damage to lung tissues. Although immune cells called macrophages are known to be involved in this phenomenon, not all the mechanisms involved are well understood.

Now, a team of researchers from the Federal Polytechnic University of Zurich has found a key piece in mice that helps to understand why the elderly are especially vulnerable to viral respiratory infections. The results of their work, published in the journal Science Immunologyshow that the origin of the macrophages in the lungs determines the severity of the disease.

Macrophages are cells that are part of the innate immune system and act early when pathogens and various foreign substances appear in the body. These white blood cells originate from monocytes (immune cells that travel through the blood) when they leave the blood vessels and migrate to different tissues. Macrophages are responsible for devouring (phagocytizing) and destroying cell debris as well as bacteria and viruses, which is why they are considered “cleaning” cells. In addition, they also communicate with other defensive cells to warn of the presence of infectious agents by releasing messenger molecules (cytokines).

The new research has found in mice that the replacement of the normal population of macrophages residing in the alveoli (hemispherical cavities in the lungs where gas exchange occurs) by bone marrow-derived macrophages leads to a serious respiratory infection.

Under normal conditions, the macrophages that remain in the lungs of mice and humans come from fetal monocytes that developed in the liver during the embryonic stage. These macrophages play a vital role in defense against viral infections. However, certain infections such as those caused by type A influenza viruses can drastically reduce the number of macrophages (since they die in the defense process). Before the results of this research were published, it was unknown what origin the new immune cells that repopulated the lungs had and what consequences the death of a large part of the macrophages in the lungs had for later viral infections. Furthermore, the origin of alveolar macrophages was thought not to influence their function.

The researchers, however, have verified that the origin of the aforementioned immune cells is essential in the response to viral respiratory infections, which refutes the prevailing belief to date. To delve into this question, they used different mouse models and also specific markers to identify macrophages derived from fetal monocytes and those from bone marrow. In turn, they also observed what happened to each population of macrophages after repeated infections with influenza A viruses or with the aging of the mice.

Initially, it is the lungs’ own macrophages that multiplied and restored the number of immune cells in the lungs after a viral infection. However, over the months, the macrophages that came from the bone marrow ended up “invading” the alveoli because they had a greater capacity to multiply. On the other hand, the ‘invading’ macrophages triggered a further inflammatory response, including a cytokine storm, which caused damage to the lungs. This change in the populations of macrophages, with a predominance of those that come from the bone marrow, also occurred progressively with the aging of the mice, even though they had never had the flu.

The consequence of the different origin of the macrophages in the lungs was that the mice suffered more severe influenza and died more. In fact, when alveolar macrophages from old mice (which came from the bone marrow) were transplanted into young animals, the latter also suffered a worse evolution of the flu, with a higher risk of death.

The authors explain that their research findings are similar to those of other studies that have looked at the lungs of people who have had severe COVID-19. SARS-CoV-2 infected patients with mild disease usually have a nearly intact alveolar macrophage population, whereas those with severe infection have inflammatory macrophages originating from the bone marrow. The next step in this research is to find out what molecular mechanisms cause the death of macrophages residing in the alveoli.

Esther Samper

Reference: “Monocyte-​derived alveolar macrophages autonomously determine severe outcome of respiratory viral infection”, Fengqi Li et al. in Science Immunology, vol. 7, no. 73, July 1, 2022.


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