Severe flu risk as immune cells swap with age

Immunology and Science (2022). DOI: 10.1126 / sciimmunol.abj5761 “width =” 800 “height =” 335 “/>

AM and Mo cells found in influenza mice. Reconstituted FeMo Csf2ra – / – and mice WT were infected with IAV (20 pfu PR8) as shown in Fig. 2A. The representative gates and BAL AM and Bmo-Mac dots are displayed on d10 and d21 pi Data represent at least 3 independent tests with n = 3 mice of each group at each time point. Credit: Immunology (2022). DOI: 10.1126 / sciimmunol.abj5761

Lung infections with influenza virus or coronavirus frequently cause severe progression in the elderly. This is due to the large number of tumors that cause damage to the lungs. The exact cause has not yet been announced. Macrophages, also known as immune system viruses, play a role. They release inflammatory agents, which in turn trigger a severe immune response.

A team of researchers led by Manfred Kopf, an Immunologist and Professor of Molecular Biomedicine at ETH Zurich, showed that in mice that originated in the lungs – the so-called embryonic alveolar. macrophages– die quickly when animals are infected with the flu virus and are replaced after a few days by macrophages from bones. The more severe the infection, the greater the number of embryonic alveolar macrophages dying. ETH immunization experts recently reported their findings in the journal Immunology.

Differences in function and development of diseases

Macrophages have many functions, including the first line of protection against infections. Depending on the biology of development, they can almost be divided into two groups. In humans and in mice, all organs and tissues have permanent macrophages that were already formed at the time. embryonic development in the fetal liver and perform specific functions in a variety of tissues. The embryonic macrophages in the lungs enter the main oxygen-carbon chain that occurs in the alveoli.

The second group of macrophages appear during blood formation in the bones and migrate through the bloodstream to different tissues, where they grow into specific macrophages.

“Once again, it is thought that macrophages derived from bone marrow have the same function as alveolar macrophages originating in the fetal liver, and this is true for all tissues,” said Federica Piattini and Fengqi Li, those in the Kopf research group. and both the original authors of the paper. They have now refuted this hypothesis, suggesting that, in fact, macrophages derived from bone cause damage in cases of lung infection.

Two researchers created two groups of mice: one group had alveolar macrophages that formed during embryonic stage, and the other had acquired macrophages of bone. When they become infected influenza, mice that received alveolar macrophages from the bones became very ill and died. One of the reasons for the development of severe disease is that these macrophages cause a malignant tumor (cytokine storm).

The authors concluded that the origin of macrophages plays an important role in the development of the disease. They also showed that influenza in mice stimulates alveolar macrophages.

Evidence of a similar process with COVID-19

According to the researchers, it is more effective and efficient compared to their experiments on mice and coronavirus infections in humans. “It appears that a similar process occurs in the case of COVID-19,” Kopf said. One previous study reported that embryonic lung macrophages were highly stored in COVID-19 patients with mild disease progression, while severe disease was associated with alveolar inflammation. macrophages that originate from bones.

However, it appears that embryonic alveolar macrophages are not replaced only in severe cases of infection. Kopf suggests that this mutation also occurs in older mice, even if they have never been infected before. Transplantation of alveolar macrophages from adult to small mice resulted in severe influenza development that ended in death.

It is known that there is a risk of severe influenza or COVID-19 in it great people. “Obviously there are many reasons for this,” Kopf said. New data, however, suggest that the loss of embryonic macrophages over a lifetime plays a role here.

Professor ETH and his team are now planning to study molecular mechanisms of fetal death alveolar macrophages.

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Learn more:
Fengqi Li et al, Monocyte-derived alveolar macrophages autonomously determine the potential effect of respiratory viral infection, Immunology (2022). DOI: 10.1126 / sciimmunol.abj5761

hintThe risk of severe flu as immunizations change with age (2022, July 8) was recovered on July 8, 2022 from .html

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