Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis.
Nat Immunol
; 24(5): 767-779, 2023 05.
Article
in English
| MEDLINE | ID: covidwho-20238331
ABSTRACT
Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladaptive response during sepsis. We generated a whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune response that identified populations of immunosuppressive mature and immature neutrophils. In co-culture, CD66b+ sepsis neutrophils inhibited proliferation and activation of CD4+ T cells. Single-cell multiomic mapping of circulating hematopoietic stem and progenitor cells (HSPCs) (29,366 cells, n = 27) indicated altered granulopoiesis in patients with sepsis. These features were enriched in a patient subset with poor outcome and a specific sepsis response signature that displayed higher frequencies of IL1R2+ immature neutrophils, epigenetic and transcriptomic signatures of emergency granulopoiesis in HSPCs and STAT3-mediated gene regulation across different infectious etiologies and syndromes. Our findings offer potential therapeutic targets and opportunities for stratified medicine in severe infection.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sepsis
/
Neutrophils
Type of study:
Etiology study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Nat Immunol
Journal subject:
Allergy and Immunology
Year:
2023
Document Type:
Article
Affiliation country:
S41590-023-01490-5
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