Multi-omic Studies of Neutrophils Reveal Programmed Deactivation Phenotypes After Inflammatory Stimulus
type: CreativeWork
description: Neutrophils serve as a critical first line of defence against bacterial invasion, and their dysfunction is associated with unfavourable clinical outcomes. A detailed understanding of the activation and resolution pathways that modulate neutrophil interactions with bacteria, as well as the alterations that occur in dysfunctional states, will help develop the existing knowlege on the pathobiology of infection. This knowledge may also pave the way for the development of innovative, non-antibiotic therapeutic strategies. A comprehensive time-course multi-omics study was conducted to evaluate the neutrophil response to a common human pathogen Staphylococcus aureus. This was undertaken using a model of healthy human neutrophils exposed to heat-killed, labelled S. aureus particles with the objective of identifying candidate pathways that underpin the antimicrobial responses of these cells. The methodologies employed in this investigation include proteome, phosphoproteome, kinome, and transcriptome profiling. Data interpretation was facilitated through clustering and pathway enrichment analysis. This multi-omic approach was complemented by a multi-parametric assay of neutrophil functions. Analysis of the phosphoproteome revealed a bimodal response pattern characterized by peak phosphorylation or dephosphorylation at 15 and 120 minutes, indicating distinct early and late phases of response. Within the enriched pathways associated with phosphorylated proteins, phagocytosis and degranulation were prevalent, while mRNA processing emerged as the consensus term among dephosphorylated proteins. These findings were corroborated at the kinase level, where active kinases were predominantly engaged in bactericidal and transcriptional functions at 15 minutes. In contrast, a broad suppression of kinase activity was observed at 120 minutes. Complementary RNA sequencing data illustrated a biphasic response, with early transcripts (at 15 minutes) associated with the initiation of inflammat…
abstract: Neutrophils serve as a critical first line of defence against bacterial invasion, and their dysfunction is associated with unfavourable clinical outcomes. A detailed understanding of the activation and resolution pathways that modulate neutrophil interactions with bacteria, as well as the alterations that occur in dysfunctional states, will help develop the existing knowlege on the pathobiology of infection. This knowledge may also pave the way for the development of innovative, non-antibiotic therapeutic strategies. A comprehensive time-course multi-omics study was conducted to evaluate the neutrophil response to a common human pathogen Staphylococcus aureus. This was undertaken using a model of healthy human neutrophils exposed to heat-killed, labelled S. aureus particles with the objective of identifying candidate pathways that underpin the antimicrobial responses of these cells. The methodologies employed in this investigation include proteome, phosphoproteome, kinome, and transcriptome profiling. Data interpretation was facilitated through clustering and pathway enrichment analysis. This multi-omic approach was complemented by a multi-parametric assay of neutrophil functions. Analysis of the phosphoproteome revealed a bimodal response pattern characterized by peak phosphorylation or dephosphorylation at 15 and 120 minutes, indicating distinct early and late phases of response. Within the enriched pathways associated with phosphorylated proteins, phagocytosis and degranulation were prevalent, while mRNA processing emerged as the consensus term among dephosphorylated proteins. These findings were corroborated at the kinase level, where active kinases were predominantly engaged in bactericidal and transcriptional functions at 15 minutes. In contrast, a broad suppression of kinase activity was observed at 120 minutes. Complementary RNA sequencing data illustrated a biphasic response, with early transcripts (at 15 minutes) associated with the initiation of inflammat…
author: Iqbal, Muhammad
keywords: Deactivation Phenotypes, Kinome Profiling, Multi-omics, Neutrophil, Proteomics, RNAseq, Staphylococcus aureus
license: https://www.repository.cam.ac.uk/bitstreams/f8a3004d-60cd-4361-84dd-d48ab20f20e8/download
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
date published: 2025-02-18
date modified: 2026-07-22T22:23:56Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.119840