Innate immune system is profoundly reprogrammed – healing practice

Long-lasting and profound reprogramming of immune cells

The reaction of the immune system to an infection with SARS-CoV-2 has a significant impact on the course of COVID-19 and an excessive immune response is held responsible for various threatening complications. A new study makes it clear which far-reaching changes the virus triggers in the innate immune system.

The research team around first author Dr. Sebastian Theobald from Cologne University Hospital examined the effect of spike protein, a typical feature of the coronavirus, on the innate immune system. It turned out that a SARS-CoV-2 infection causes “profound and long-lasting reprogramming of macrophages,” the researchers write. The corresponding study results were published in the specialist magazine “EMBO Molecular Medicine”.

Critical release of cytokines

Why some infected people react with an excessive immune response to SARS-CoV-2 is still not well understood, according to the researchers. It is clear that the SARS-CoV-2 infection can lead to the massive release of inflammatory signal substances, so-called cytokines, which cause severe organ damage in some infected people and lure further, activated defense cells into the tissue in a chain reaction. How the virus triggers the release of cytokines has not been clearly established.

Response to the spike protein investigated

For the first time, the researchers were able to demonstrate the effect of spike protein on the innate immune system and they found that human defense cells (macrophages, also called scavenger cells) are massively stimulated by the viral spike protein to produce the inflammatory signaling substance interleukin 1.

However, this was only the case if the macrophages of COVID-19 infected people were examined in the experiments. Macrophages from people who have not yet had contact with SARS-CoV-2 did not react by releasing interleukin 1, the researchers report.

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Very unusual immune response

“This selective immune response of a classic signaling pathway of the innate immune system is very unusual and has not yet been described in this way,” emphasizes Dr. Jan Rybniker, head of the infectious disease research laboratory at Cologne University Hospital. The expert also sees “many starting points here to understand why some people react with an excessive reaction of the immune system.”

Epigenetic changes detectable

Interestingly, the macrophages could still be activated very strongly by the spike protein several weeks to months after a SARS-CoV-2 infection, the researchers further report. “Since macrophages have a very short lifespan of just a few days, this suggests changes in the DNA of macrophage progenitor cells,” explains Dr. Sebastian Theobald. The researchers were also able to demonstrate these so-called epigenetic changes through complex sequencing experiments.

The profound changes from macrophages to the genetic makeup of the cells can now also be used to better understand the long-term consequences of COVID-19, the research team continues. Last but not least, the study results are also important in relation to the vaccines, as spike protein plays a key role in these.

“For the success of the various vaccine constructs, it is certainly beneficial that the spike protein leads to a strong activation of the innate immune system,” says Rybniker.

In addition, the inflammasome signaling pathway investigated here, which ultimately leads to the release of interleukin 1, is also considered a possible therapeutic starting point for immunomodulatory therapies in severe COVID-19 courses, and the study provides a scientific basis for this. (fp)

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Author and source information

This text complies with the requirements of specialist medical literature, medical guidelines and current studies and has been checked by medical professionals.


  • Sebastian J. Theobald, Alexander Simonis, Theodoros Georgomanolis, Christoph Kreer, Matthias Zehner, Hannah S. Eisfeld, Marie-Christine Albert, Jason Chhen, Susanne Motameny, Florian Erger, Julia Fischer, Jakob J. Malin, Jessica Gräb, Sandra Winter, Andromachi Pouikli, Friederike David, Boris Böll, Philipp Koehler, Kanika Vanshylla, Henning Gruell, Isabelle Suárez, Michael Hallek, Gerd Fätkenheuer, Norma Jung, Oliver A. Cornely, Clara Lehmann, Peter Tessarz, Janine Altmüller, Peter Nürnberg, Hamid Kashkar, Florian Klein, Manuel Koch, Jan Rybniker: Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19; in: EMBO Molecular Medicine (published June 16, 2021),
  • University Hospital Cologne: Long and profound reprogramming of immune cells (published June 16, 2021),

Important NOTE:
This article is for general guidance only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor.



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