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Transcriptional profiling links unique human macrophage phenotypes to the growth of intracellular Salmonella enterica serovar Typhi

Schade, Ruth ; Butler, Daniel S.C. LU ; McKenna, Joy A. ; Di Luccia, Blanda ; Shokoohi, Vida ; Hamblin, Meagan ; Pham, Trung H.M. and Monack, Denise M. (2024) In Scientific Reports 14. p.1-15
Abstract

Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing... (More)

Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.

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author
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publishing date
type
Contribution to journal
publication status
published
in
Scientific Reports
volume
14
article number
12811
pages
1 - 15
publisher
Nature Publishing Group
external identifiers
  • pmid:38834738
  • scopus:85195244145
ISSN
2045-2322
DOI
10.1038/s41598-024-63588-6
language
English
LU publication?
no
additional info
Publisher Copyright: © The Author(s) 2024.
id
5b4af1e2-9c2a-400c-acda-a291f25bee87
date added to LUP
2026-09-09 15:42:50
date last changed
2026-09-10 08:18:15
@article{5b4af1e2-9c2a-400c-acda-a291f25bee87,
  abstract     = {{<p>Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.</p>}},
  author       = {{Schade, Ruth and Butler, Daniel S.C. and McKenna, Joy A. and Di Luccia, Blanda and Shokoohi, Vida and Hamblin, Meagan and Pham, Trung H.M. and Monack, Denise M.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  pages        = {{1--15}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Transcriptional profiling links unique human macrophage phenotypes to the growth of intracellular Salmonella enterica serovar Typhi}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-63588-6}},
  doi          = {{10.1038/s41598-024-63588-6}},
  volume       = {{14}},
  year         = {{2024}},
}