Complement activation induces excessive T cell cytotoxicity in severe COVID-19

被引：0

作者：

Georg, Philipp ^{[1
,2
,3
]}

Astaburuaga-Garcia, Rosario ^{[4
,5
]}

Bonaguro, Lorenzo ^{[6
,7
]}

Brumhard, Sophia ^{[1
,2
,3
]}

Michalick, Laura ^{[8
]}

Lippert, Lena J. ^{[1
,2
,3
]}

Kostevc, Tomislav ^{[9
]}

Gaebel, Christiane ^{[9
]}

Schneider, Maria ^{[9
]}

Streitz, Mathias ^{[9
]}

Demichev, Vadim ^{[10
,11
,12
]}

Gemuend, Ioanna ^{[6
,13
,14
]}

Barone, Matthias ^{[9
]}

Tober-Lau, Pinkus ^{[1
,2
,3
]}

Helbig, Elisa T. ^{[1
,2
,3
]}

Hillus, David ^{[1
,2
,3
]}

Petrov, Lev ^{[9
]}

Stein, Julia ^{[9
]}

Dey, Hannah-Philine ^{[9
]}

Paclik, Daniela ^{[9
]}

Iwert, Christina ^{[9
]}

Muelleder, Michael ^{[15
]}

Aulakh, Simran Kaur ^{[10
]}

Djudjaj, Sonja ^{[16
]}

Buelow, Roman D. ^{[16
]}

Mei, Henrik E. ^{[17
]}

Schulz, Axel R. ^{[17
]}

Thiel, Andreas ^{[2
,3
,18
,19
,20
]}

Hippenstiel, Stefan ^{[1
,2
,3
]}

Saliba, Antoine-Emmanuel ^{[21
]}

Eils, Roland ^{[22
,23
]}

Lehmann, Irina ^{[22
,23
]}

Mall, Marcus A. ^{[23
,24
,25
]}

Stricker, Sebastian ^{[24
]}

Roehmel, Jobst ^{[24
]}

Corman, Victor M. ^{[26
]}

Beule, Dieter ^{[27
]}

Wyler, Emanuel ^{[28
]}

Landthaler, Markus ^{[5
,28
]}

Obermayer, Benedikt ^{[27
]}

von Stillfried, Saskia ^{[16
]}

Boor, Peter ^{[16
,29
,30
]}

Demir, Munevver ^{[31
]}

Wesselmann, Hans ^{[1
,2
,3
]}

Suttorp, Norbert ^{[1
,2
,3
,32
]}

Uhrig, Alexander ^{[1
,2
,3
]}

Mueller-Redetzky, Holger ^{[1
,2
,3
]}

Nattermann, Jacob ^{[33
]}

Kuebler, Wolfgang M. ^{[8
]}

Meisel, Christian ^{[9
,34
]}

机构：

[1] Charite Univ Med Berlin, Dept Infect Dis & Resp Med, Berlin, Germany

[2] Free Univ Berlin, Berlin, Germany

[3] Humboldt Univ, Berlin, Germany

[4] Charite Univ Med Berlin, Inst Pathol, Berlin, Germany

[5] Humboldt Univ, IRI Life Sci, Berlin, Germany

[6] Univ Bonn, Life & Med Sci LIMES Inst, Genom & Immunoregulat, Bonn, Germany

[7] Deutsch Zentrum Neurodegenerativen Erkrankungen D, Syst Med, Bonn, Germany

[8] Charite Univ Med Berlin, Inst Physiol, Berlin, Germany

[9] Charite Univ Med Berlin, Inst Med Immunol, Berlin, Germany

[10] Francis Crick Inst, Mol Biol Metab Lab, London, England

[11] Charite Univ Med Berlin, Dept Biochem, Berlin, Germany

[12] Univ Cambridge, Cambridge Ctr Prote, Dept Biochem, Cambridge, England

[13] Univ Bonn, PRECISE Platform Genom & Epigen, DZNE, Bonn, Germany

[14] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia

[15] Charite Univ Med Berlin, High Throughput Mass Spectrometry, Core Facil, Berlin, Germany

[16] Rhein Westfal TH Aachen, Inst Pathol, Univ Clin Aachen, Aachen, Germany

[17] DRFZ Berlin, Mass Cytometry Lab, Berlin, Germany

[18] Tech Univ Berlin, Si M Simulierte Mensch Sci Framework, Berlin, Germany

[19] Charite Univ Med Berlin, Berlin, Germany

[20] Berlin Inst Hlth, Berlin, Germany

[21] Helmholtz Ctr Infect Res HZI, Helmholtz Inst RNA Based Infect Res HIRI, Wurzburg, Germany

[22] Charite Univ Med Berlin, Berlin Inst Hlth BIH, Ctr Digital Hlth, Berlin, Germany

[23] German Ctr Lung Res DZL, Berlin, Germany

[24] Charite Univ Med Berlin, Dept Pediat Resp Med Immunol & Crit Care Med, Berlin, Germany

[25] Charite Univ Med Berlin, Berlin Inst Hlth BIH, Berlin, Germany

[26] Charite Univ Med Berlin, Inst Virol, Berlin, Germany

[27] Charite Univ Med Berlin, Core Unit Bioinformat, Berlin Inst Hlth BIH, Berlin, Germany

[28] Helmholtz Assoc, Berlin Inst Med Syst Biol, Max Delbruck Ctr Mol Med, Berlin, Germany

[29] Rhein Westfal TH Aachen, Dept Nephrol, Univ Clin Aachen, Aachen, Germany

[30] Rhein Westfal TH Aachen, Univ Clin Aachen, Electron Microscopy Facil, Aachen, Germany

[31] Charite Univ Med Berlin, Dept Hepatol & Gastroenterol, Berlin, Germany

[32] German Ctr Lung Res DZL, Giessen, Germany

[33] Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany

[34] Charite Vivantes, Labor Berlin, Dept Immunol, Berlin, Germany

[35] Radboud Univ Nijmegen Med Ctr, Radboud Ctr Infect Dis, Dept Internal Med, Nijmegen, Netherlands

[36] Univ Med Ctr Hamburg Eppendorf, Bernhard Nocht Inst Trop Med, Dept Trop Med, Dept Med 1, Hamburg, Germany

来源：

CELL | 2022年 / 185卷 / 03期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

R PACKAGE; NK CELLS; REVEALS; EXPRESSION; INFERENCE; INNATE;

D O I：

10.1016/j.cel.2021.12.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16(+) T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16(+) T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16(+) T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16(+) cytotoxic T cells. Proportions of activated CD16(+) T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

引用

页码：493 / +

页数：46

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