Home Latest News News Bei schwer erkrankten COVID-19 Patient:innen hemmen SARS-CoV-2 Viren die Immunantwort, indem sie den Botenstoff TGFβ induzieren
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The SARS-CoV-2 virus inhibits the immune response by inducing the cytokine TGFβ in COVID-19 patients with severe disease

Researchers at the DRFZ and the Charité University Medicine Berlin have investigated the reasons why some patients suffer from a severe COVID-19 disease course. The result is surprising: the Corona virus induces the expression of the cytokine TGFβ in these patients, which inhibits their immune system. Usually, TGFβ is only produced at the end of an immune reaction in order to terminate it. However, in COVID-19 patients with severe disease, TGFβ is produced from the beginning of the immune response. This inactivates the Natural Killer (NK) cells that would normally recognize and kill virus-infected cells, thereby inhibiting the replication of the virus. This research has now been published in the journal NATURE (Witkowski et al.).  The same researchers have previously shown that the cells producing antibodies are also affected by the cytokine TGFβ, resulting in a chronic immune reaction, that is no longer directed against the virus (Ferreira-Gomez, Nature Communications 2021). TGFβ is also likely to be involved in the formation of thromboses and fibroses. These results open up a new opportunity to detect severe cases of COVID-19 from the outset, through monitoring of early TGFβ production, and then possibly also to mitigate such severe disease, through therapeutic inhibition of this cytokine.

Publications

Untimely TGFβ 1 responses in severe COVID-19 limit antiviral function of NK cells
M. Witkowski, C.Tizian, M. Ferreira-Gomes, D. Niemeyer, T. C. Jones, F. Heinrich, S. Frischbutter, S. Angermair, T. Hohnstein, I. Mattiola, P. Nawrath, S. Mc Ewen, S. Zocche, E. Viviano, G. A. Heinz, M. Maurer, U. Kölsch, R. L. Chua, T. Aschman, C. Meisel, J. Radke15, B. Sawitzki, J. Roehmel, K. Allers, V.Moos, T.Schneider, L. Hanitsch, M. A. Mall, C. Conrad, H. Radbruch, C.U. Duerr, J. A. Trapan, E. Marcenaro, T. Kallinich, V. M. Corman, F. Kurth, L. E. Sander, C. Drosten, S. Treskatsch, P.Durek, A. Kruglov, A. Radbruch, M.F. Mashreghi*, and Andreas Diefenbach* (contributed equaly); Nature, in press 2021, doi: 10.1038/s41586-021-04142-6
Clues that natural killer cells help to control COVID
News and Views in Nature by Emilie Narni-Mancinelli & Eric Vivier
SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself
Ferreira-Gomes, M., Kruglov, A., Durek, P., Heinrich, F., Tizian, C., Heinz, G. A., Pascual-Reguant, A., Du, W., Mothes, R., Fan, C., Frischbutter, S., Habenicht, K., Budzinski, L., Ninnemann, J., Jani, P. K., Guerra, G., Lehmann, K., Matz, M., Ostendorf, L., Heiberger, L., Chang, H.-D., Bauherr, S., Maurer, M., Schoenrich, G., Raftery, M., Kallinich, T., Mall, M. A., Angermair, S., Treskatsch, S., Doerner, T., Corman, V. M., Diefenbach, A., Volk, H.-D., Elezkurtaj, S., Winkler, T. H., Dong, J., Hauser, A. E., Radbruch, H., Witkowski, M., Melchers, F., Radbruch, A., Mashreghi, M.-F. Nat Commun 12, 1961 (2021). https://doi.org/10.1038/s41467-021-22210-3

Media response

Press release by Charité – University Medicine
Nature-Studie: SARS-CoV-2 bringt Timing der Immunreaktion durcheinander
Charité- und DRFZ-Studie zeigt: So kommt es zu schweren Covid-Verläufen
Interview mit Mir-Farzin-Mashreghi in gmx.net: Wie das SARS-CoV-2 Virus das Immunsystem austrickst und so schwere Covid-19 Verläufe verursacht.
mdr WISSEN - die grossen Fragen unserer Zeit
Schwere Covid-19-Verläufe: Wie das Immunsystem verwirrt wird
wissenschaft.de
Covid-19
Gestörtes Immun-Timing bei schweren Fällen
Berliner Zeitung
Falsches Timing: Berliner Forscher finden Ursache für schwere Covid-Verläufe
VBIO
Aktuelles aus Biologie, Biowissenschaften & Biomedizin -
SARS-CoV-2 bringt Timing der Immunreaktion durcheinander
Technology Networks - Analysis & Separations
Immune Response Timings Disrupted by SARS-CoV-2
Published: October 26, 2021

Contact

Development of the immune system Prof. Dr. Andreas Diefenbach Phone +49 30 450 524 171 andreas.diefenbach@charite.de more
Therapeutic Gene Regulation || Regine von Ramin Lab Molecular Rheumatology || BCRT/DRFZ Single-Cell Laboratory for Advanced Cellular Therapies Dr. Mir-Farzin Mashreghi Phone +49 (0)30 28460-752 mashreghi@drfz.de more
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