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In vivo regulation of the monocyte phenotype by Mycobacterium marinum and the ESX-1 type VII secretion system

Munke, Kristina LU ; Wulff, Line ; Lienard, Julia LU ; Carlsson, Fredric LU orcid and Agace, William W. LU (2025) In Scientific Reports 15(1).
Abstract

Pathogenic mycobacteria require the conserved ESX-1 type VII secretion system to cause disease. In a murine Mycobacterium marinum infection model we previously demonstrated that infiltrating monocytes and neutrophils represent the major bacteria-harbouring cell populations in infected tissue. In the current study we use this model, in combination with scRNA sequencing, to assess the impact of M. marinum infection on the transcriptional profile of infiltrating Ly6C⁺MHCII⁺ monocytes in vivo. Our findings demonstrate that infection of infiltrating monocytes with M. marinum alters their cytokine expression profile, induces glycolytic metabolism, hypoxia-mediated signaling, nitric oxide synthesis, tissue remodeling, and suppresses... (More)

Pathogenic mycobacteria require the conserved ESX-1 type VII secretion system to cause disease. In a murine Mycobacterium marinum infection model we previously demonstrated that infiltrating monocytes and neutrophils represent the major bacteria-harbouring cell populations in infected tissue. In the current study we use this model, in combination with scRNA sequencing, to assess the impact of M. marinum infection on the transcriptional profile of infiltrating Ly6C⁺MHCII⁺ monocytes in vivo. Our findings demonstrate that infection of infiltrating monocytes with M. marinum alters their cytokine expression profile, induces glycolytic metabolism, hypoxia-mediated signaling, nitric oxide synthesis, tissue remodeling, and suppresses responsiveness to IFNγ. We further show that the transcriptional response of bystander monocytes is influenced by ESX-1-dependent mechanisms, including a reduced responsiveness to IFNγ. These findings suggest that mycobacterial infection has pleiotropic effects on monocyte phenotype, with potential implications in bacterial growth restriction and granuloma formation.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
15
issue
1
article number
4545
publisher
Nature Publishing Group
external identifiers
  • pmid:39915532
  • scopus:85218204533
ISSN
2045-2322
DOI
10.1038/s41598-025-88212-z
language
English
LU publication?
yes
id
98cf5a1a-c1e9-4b8d-9a2b-0f22af441eda
date added to LUP
2025-06-10 08:30:05
date last changed
2025-07-08 11:27:05
@article{98cf5a1a-c1e9-4b8d-9a2b-0f22af441eda,
  abstract     = {{<p>Pathogenic mycobacteria require the conserved ESX-1 type VII secretion system to cause disease. In a murine Mycobacterium marinum infection model we previously demonstrated that infiltrating monocytes and neutrophils represent the major bacteria-harbouring cell populations in infected tissue. In the current study we use this model, in combination with scRNA sequencing, to assess the impact of M. marinum infection on the transcriptional profile of infiltrating Ly6C⁺MHCII⁺ monocytes in vivo. Our findings demonstrate that infection of infiltrating monocytes with M. marinum alters their cytokine expression profile, induces glycolytic metabolism, hypoxia-mediated signaling, nitric oxide synthesis, tissue remodeling, and suppresses responsiveness to IFNγ. We further show that the transcriptional response of bystander monocytes is influenced by ESX-1-dependent mechanisms, including a reduced responsiveness to IFNγ. These findings suggest that mycobacterial infection has pleiotropic effects on monocyte phenotype, with potential implications in bacterial growth restriction and granuloma formation.</p>}},
  author       = {{Munke, Kristina and Wulff, Line and Lienard, Julia and Carlsson, Fredric and Agace, William W.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{In vivo regulation of the monocyte phenotype by Mycobacterium marinum and the ESX-1 type VII secretion system}},
  url          = {{http://dx.doi.org/10.1038/s41598-025-88212-z}},
  doi          = {{10.1038/s41598-025-88212-z}},
  volume       = {{15}},
  year         = {{2025}},
}