PUBLICATION

Dynamics of macrophage polarization support Salmonella persistence in a whole living organism

Authors
Leiba, J., Sipka, T., Begon-Pescia, C., Bernardello, M., Tairi, S., Bossi, L., Gonzalez, A.A., Mialhe, X., Gualda, E., Loza-Alvarez, P., Blanc-Potard, A., Lutfalla, G., Nguyen-Chi, M.E.
ID
ZDB-PUB-240116-1
Date
2024
Source
eLIFE   13: (Journal)
Registered Authors
Bernardello, Matteo, Gualda, Emilio, Loza-Alvarez, Pablo, Lutfalla, Georges
Keywords
infectious disease, microbiology, zebrafish
Datasets
GEO:GSE224985
MeSH Terms
  • Animals
  • Host-Pathogen Interactions*
  • Macrophages/microbiology
  • Phenotype
  • Salmonella typhimurium
  • Zebrafish*
PubMed
38224094 Full text @ Elife
Abstract
Numerous intracellular bacterial pathogens interfere with macrophage function, including macrophage polarization, to establish a niche and persist. However, the spatiotemporal dynamics of macrophage polarization during infection within host remain to be investigated. Here, we implement a model of persistent Salmonella Typhimurium infection in zebrafish, which allows visualization of polarized macrophages and bacteria in real time at high-resolution. While macrophages polarize toward M1-like phenotype to control early infection, during later stages, Salmonella persists inside non-inflammatory clustered macrophages. Transcriptomic profiling of macrophages showed a highly dynamic signature during infection characterized by a switch from pro-inflammatory to anti-inflammatory/pro-regenerative status and revealed a shift in adhesion program. In agreement with this specific adhesion signature, macrophage trajectory tracking identifies motionless macrophages as a permissive niche for persistent Salmonella. Our results demonstrate that zebrafish model provides a unique platform to explore, in a whole organism, the versatile nature of macrophage functional programs during bacterial acute and persistent infections.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Antibodies
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Mapping