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

Autor: Upasana Parthasarathy, Yi Kuang, Gunjan Thakur, John D. Hogan, Thomas P. Wyche, James E. Norton, Jr., Jason R. Killough, Theodore R. Sana, Caroline Beakes, BaoJen Shyong, Rena N. Zhang, Dario A. Gutierrez, Michael Filbin, David C. Christiani, Alex G. Therien, Christopher H. Woelk, Cory H. White, Roberta Martinelli
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iScience, Vol 26, Iss 2, Pp 105948- (2023)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2023.105948
Popis: 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.
Databáze: Directory of Open Access Journals