Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19

被引：97

作者：

Theobald, Sebastian J. ^{[1
,2
,3
,4
]}

Simonis, Alexander ^{[1
,2
,3
,4
]}

Georgomanolis, Theodoros ^{[3
,5
]}

Kreer, Christoph ^{[2
,6
]}

Zehner, Matthias ^{[2
,6
]}

Eisfeld, Hannah S. ^{[1
,2
,3
,4
]}

Albert, Marie-Christine ^{[7
,8
]}

Chhen, Jason ^{[1
,2
,3
,4
]}

Motameny, Susanne ^{[3
,5
]}

Erger, Florian ^{[3
,5
,9
]}

Fischer, Julia ^{[1
,2
,3
,4
,10
]}

Malin, Jakob J. ^{[1
,2
,3
,4
]}

Graeb, Jessica ^{[1
,2
,3
,4
]}

Winter, Sandra ^{[1
,2
,3
,4
]}

Pouikli, Andromachi ^{[11
]}

David, Friederike ^{[3
,5
]}

Boell, Boris ^{[1
,2
]}

Koehler, Philipp ^{[1
,2
,3
,4
,7
]}

Vanshylla, Kanika ^{[2
,6
]}

Gruell, Henning ^{[2
,6
]}

Suarez, Isabelle ^{[1
,2
,10
]}

Hallek, Michael ^{[1
,2
]}

Faetkenheuer, Gerd ^{[1
,2
,10
]}

Jung, Norma ^{[1
,2
,10
]}

Cornely, Oliver A. ^{[1
,2
,3
,4
,7
,10
]}

Lehmann, Clara ^{[1
,2
,3
,4
,10
]}

Tessarz, Peter ^{[7
,11
]}

Altmueller, Janine ^{[3
,5
]}

Nuernberg, Peter ^{[3
,4
,5
]}

Kashkar, Hamid ^{[7
,8
]}

Klein, Florian ^{[2
,6
,10
]}

Koch, Manuel ^{[12
,13
]}

Rybniker, Jan ^{[1
,2
,3
,4
,10
]}

机构：

[1] Univ Cologne, Fac Med, Dept Internal Med 1, Cologne, Germany

[2] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[3] Univ Cologne, Fac Med, Cologne, Germany

[4] Univ Cologne, Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany

[5] Univ Cologne, Univ Hosp Cologne, Cologne Ctr Genom CCG, Cologne, Germany

[6] Univ Cologne, Fac Med, Inst Virol, Lab Expt Immunol, Cologne, Germany

[7] Univ Cologne, Excellence Cluster Cellular Stress Responses Agin, Cologne, Germany

[8] Univ Cologne, Inst Med Microbiol Immunol & Hyg IMMIH, Cologne, Germany

[9] Univ Hosp Cologne, Fac Med, Inst Human Genet, Cologne, Germany

[10] German Ctr Infect Res DZIF, Partner Site Bonn Cologne, Cologne, Germany

[11] Max Planck Inst Biol Ageing, Max Planck Res Grp Chromatin & Ageing, Cologne, Germany

[12] Univ Cologne, Med Fac, Inst Dent Res & Oral Musculoskeletal Biol, Cologne, Germany

[13] Univ Cologne, Med Fac, Ctr Biochem, Cologne, Germany

来源：

EMBO MOLECULAR MEDICINE | 2021年 / 13卷 / 08期

关键词：

inflammasome; innate immunity; macrophage; NLRP3; SARS-CoV-2; NLRP3; INFLAMMASOME; INDUCTION; INFECTION; RECOGNITION; EXPRESSION; IMMUNITY; NEK7;

D O I：

10.15252/emmm.202114150

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Innate immunity triggers responsible for viral control or hyperinflammation in COVID-19 are largely unknown. Here we show that the SARS-CoV-2 spike protein (S-protein) primes inflammasome formation and release of mature interleukin-1 beta (IL-1 beta) in macrophages derived from COVID-19 patients but not in macrophages from healthy SARS-CoV-2 naive individuals. Furthermore, longitudinal analyses reveal robust S-protein-driven inflammasome activation in macrophages isolated from convalescent COVID-19 patients, which correlates with distinct epigenetic and gene expression signatures suggesting innate immune memory after recovery from COVID-19. Importantly, we show that S-protein-driven IL-1 beta secretion from patient-derived macrophages requires non-specific monocyte pre-activation in vivo to trigger NLRP3-inflammasome signaling. Our findings reveal that SARS-CoV-2 infection causes profound and long-lived reprogramming of macrophages resulting in augmented immunogenicity of the SARS-CoV-2 S-protein, a major vaccine antigen and potent driver of adaptive and innate immune signaling.

引用

页数：20

共 58 条

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