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

共 50 条

[21] Activation of complement pathways and formation of membrane attack complex contribute to the development of severe COVID-19
Ellsworth, Calder
Chen, Zheng
Currey, Joshua
Xiao, Mark
Katz, Alexis R.
Wang, Chenxiao
Maness, Nicholas J.
Blair, Robert V.
Halperin, Jose H.
Kolls, Jay
Tomlinson, Stephen
Qin, Xuebin
IMMUNOBIOLOGY, 2023, 228 (05) : 33 - 33
[22] Inflammasome activation at the crux of severe COVID-19
Setu M. Vora
Judy Lieberman
Hao Wu
Nature Reviews Immunology, 2021, 21 : 694 - 703
[23] Inflammasome activation at the crux of severe COVID-19
Vora, Setu M.
Lieberman, Judy
Wu, Hao
NATURE REVIEWS IMMUNOLOGY, 2021, 21 (11) : 694 - 703
[24] Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent
Mazzoni, Alessio
Salvati, Lorenzo
Maggi, Laura
Capone, Manuela
Vanni, Anna
Spinicci, Michele
Mencarini, Jessica
Caporale, Roberto
Peruzzi, Benedetta
Antonelli, Alberto
Trotta, Michele
Zammarchi, Lorenzo
Ciani, Luca
Gori, Leonardo
Lazzeri, Chiara
Matucci, Andrea
Vultaggio, Alessandra
Rossi, Oliviero
Almerigogna, Fabio
Parronchi, Paola
Fontanari, Paolo
Lavorini, Federico
Peris, Adriano
Rossolini, Gian Maria
Bartoloni, Alessandro
Romagnani, Sergio
Liotta, Francesco
Annunziato, Francesco
Cosmi, Lorenzo
JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (09): : 4694 - 4703
[25] Role of the T cell vitamin D receptor in severe COVID-19
Kolls, Jay K.
Garry, Robert F.
NATURE IMMUNOLOGY, 2022, 23 (01) : 5 - 6
[26] Role of the T cell vitamin D receptor in severe COVID-19
Jay K. Kolls
Robert F. Garry
Nature Immunology, 2022, 23 : 5 - 6
[27] Treatment of severe COVID-19: a role for JAK and complement inhibitors?
Goury, Antoine
Mourvillier, Bruno
LANCET RESPIRATORY MEDICINE, 2023, 11 (12): : 1036 - 1037
[28] Severe COVID-19 is associated with hyperactivation of the alternative complement pathway
Boussier, Jeremy
Yatim, Nader
Marchal, Armance
Hadjadj, Jerome
Charbit, Bruno
El Sissy, Carine
Carlier, Nicolas
Pene, Frederic
Mouthon, Luc
Tharaux, Pierre-Louis
Bergeron, Anne
Smadja, David M.
Rieux-Laucat, Frederic
Duffy, Darragh
Kerneis, Solen
Fremeaux-Bacchi, Veronique
Terrier, Benjamin
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2022, 149 (02) : 550 - +
[29] T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19
Taeschler, Patrick
Adamo, Sarah
Deng, Yun
Cervia, Carlo
Zurbuchen, Yves
Chevrier, Stephane
Raeber, Miro E.
Hasler, Sara
Bachli, Esther
Rudiger, Alain
Stussi-Helbling, Melina
Huber, Lars C.
Bodenmiller, Bernd
Boyman, Onur
Nilsson, Jakob
ALLERGY, 2022, 77 (08) : 2468 - 2481
[30] Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19
Kundura, Lucy
Gimenez, Sandrine
Cezar, Renaud
Andre, Sonia
Younas, Mehwish
Lin, Yea-Lih
Portales, Pierre
Lozano, Claire
Boulle, Charlotte
Reynes, Jacques
Vincent, Thierry
Mettling, Clement
Pasero, Philippe
Muller, Laurent
Lefrant, Jean-Yves
Roger, Claire
Claret, Pierre-Geraud
Duvnjak, Sandra
Loubet, Paul
Sotto, Albert
Tran, Tu-Anh
Estaquier, Jerome
Corbeau, Pierre
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2022, 150 (03) : 594 - +

← 1 2 3 4 5 →