Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children

被引：34

作者：

Boribong, Brittany P. ^{[1
,2
,3
]}

LaSalle, Thomas J. ^{[4
,5
,6
,7
]}

Bartsch, Yannic C. ^{[3
,8
]}

Ellett, Felix ^{[9
]}

Loiselle, Maggie E. ^{[1
]}

Davis, Jameson P. ^{[1
]}

Gonye, Anna L. K. ^{[4
,5
]}

Sykes, David B. ^{[10
,11
]}

Hajizadeh, Soroush ^{[3
,4
,5
]}

Kreuzer, Johannes ^{[3
,4
]}

Pillai, Shiv ^{[3
,8
]}

Haas, Wilhelm ^{[3
,4
]}

Edlow, Andrea G. ^{[3
,12
]}

Fasano, Alessio ^{[1
,2
,3
]}

Alter, Galit ^{[3
,8
]}

Irimia, Daniel ^{[9
]}

Sade-Feldman, Moshe ^{[3
,4
,5
]}

Yonker, Lael M. ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] Massachusetts Gen Hosp, Ctr Canc Res, Dept Med, Boston, MA 02114 USA

[5] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[6] Harvard Med Sch, Program Hlth Sci & Technol, Boston, MA 02115 USA

[7] MIT, Boston, MA 02115 USA

[8] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[9] Harvard Med Sch, Ctr Engn Med & Surg, Dept Surg, Massachusetts Gen Hosp,Shriners Burns Hosp, Boston, MA 02114 USA

[10] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[11] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[12] Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA

来源：

CELL REPORTS MEDICINE | 2022年 / 3卷 / 12期

关键词：

TISSUE; ACTIVATION; EXPRESSION; SARS-COV-2; PROTEOMICS; SIGNATURE; PLATFORM;

D O I：

10.1016/j.xcrm.2022.100848

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflam-matory illness characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperin-flammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with high-ly altered metabolism that is distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanisti-cally, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.

引用

页数：22

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