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 GA, Pascual-Reguant A, Du W, Mothes R, Fan C, Frischbutter S, Habenicht KM, Budzinski L, Ninnemann J, Jani PK, Guerra GM, Lehmann K, Matz M, Ostendorf L, Heiberger L, Chang HD, Bauherr S, Maurer M, Schoenrich G, Raftery M, Kallinich T, Mall MA, Angermair S, Treskatsch S, Doerner T, Corman VM, Diefenbach A, Volk HD, Elezkurtaj S, Winkler T, Dong J, Hauser AE, Radbruch H, Witkowski M, Melchers F, Radbruch A, Mashreghi MF (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 12

Article Number: 1961

Journal Issue: 1

DOI: 10.1038/s41467-021-22210-3

Abstract

The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.

Authors with CRIS profile

Katharina Marie Habenicht Department of Medicine 5 – Haematology and Oncology Thomas Winkler Professur für Genetik

Involved external institutions

Deutsches Rheuma-Forschungszentrum (DRFZ) DE Germany (DE) Humboldt-Universität zu Berlin DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Berliner Institut für Gesundheitsforschung (BIH) DE Germany (DE)

How to cite

APA:

Ferreira-Gomes, M., Kruglov, A., Durek, P., Heinrich, F., Tizian, C., Heinz, G.A.,... Mashreghi, M.-F. (2021). SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-22210-3

MLA:

Ferreira-Gomes, Marta, et al. "SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself." Nature Communications 12.1 (2021).

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