Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, compreh...

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Bibliographic Details
Published in:	iScience Vol. 26; no. 2; p. 105948
Main Authors:	Parthasarathy, Upasana, Kuang, Yi, Thakur, Gunjan, Hogan, John D., Wyche, Thomas P., Norton, James E., Killough, Jason R., Sana, Theodore R., Beakes, Caroline, Shyong, BaoJen, Zhang, Rena N., Gutierrez, Dario A., Filbin, Michael, Christiani, David C., Therien, Alex G., Woelk, Christopher H., White, Cory H., Martinelli, Roberta
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 17-02-2023 Elsevier
Subjects:	Cell biology Components of the immune system Immunity Systems biology Cell biology Systems biology Immunity Components of the immune system
Online Access:	Get full text
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Summary:	Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in patients with sepsis. Our findings identify differentially expressed mature and immature neutrophil subsets in patients with sepsis. These subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2, and lysophosphatidylcholines, in patients with sepsis. These results enabled the construction of a statistical model based on weighted multi-omics linear regression analysis for sepsis biomarker identification. These findings could help inform early patient stratification and treatment options, and facilitate further mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites. [Display omitted] •Integrated systems immunology approach reveals unique neutrophil subsets in sepsis•Multi-omics modeling reveals biomarkers including neutrophil CD10, PTX3, and lysoPC•These findings could enable future mechanistic studies and patient stratification Immunity; Components of the immune system; Cell biology; Systems biology
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Eikon Therapeutics, New York City, NY, USA Present address: ProFound Therapeutics, Boston, MA, USA Present address: Verge Genomics, South San Francisco, CA, USA Present address: Third Rock Ventures, Boston, MA, USA These authors contributed equally Lead contact
ISSN:	2589-0042 2589-0042
DOI:	10.1016/j.isci.2023.105948