Distinct Subsets of Neutrophils Crosstalk with Cytokines and Metabolites in Patients with Sepsis

Overview

Journal iScience

Publisher Cell Press

Date 2023 Feb 9

PMID 36756375

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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