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Updated: Jul 5, 2025
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Dynamics of macrophage polarization support Salmonella persistence in a whole living organism
Jade Leiba1, Tamara Sipka1, Christina Begon-Pescia1
1LPHI, Université de Montpellier, CNRS, INSERM, Montpellier, France.
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.
Insights
Salmonella Typhimurium infection shifts macrophage polarization from pro-inflammatory to anti-inflammatory states. Persistent bacteria reside in motionless macrophages, revealing a dynamic immune response in a zebrafish model.
Area of Science:
- Immunology
- Microbiology
- Zebrafish models
Background:
- Intracellular bacteria manipulate host macrophage polarization for persistence.
- The spatiotemporal dynamics of macrophage polarization during infection are not well understood.
Purpose of the Study:
- To investigate macrophage polarization dynamics during persistent Salmonella Typhimurium infection in a live host.
- To identify host-pathogen interactions and macrophage functional states during infection.
Main Methods:
- Development of a persistent Salmonella Typhimurium infection model in zebrafish.
- Real-time, high-resolution visualization of macrophages and bacteria.
- Transcriptomic profiling of infected macrophages.
- Macrophage trajectory tracking.
Main Results:
- Macrophages initially adopt an M1-like phenotype to control early infection.
- During later stages, Salmonella persists within non-inflammatory, clustered macrophages.
- Transcriptomics reveal a dynamic shift from pro-inflammatory to anti-inflammatory/pro-regenerative macrophage states.
- Macrophage trajectory analysis identifies motionless macrophages as a niche for persistent Salmonella.
Conclusions:
- The zebrafish model allows in vivo visualization of dynamic macrophage polarization during Salmonella infection.
- Persistent Salmonella Typhimurium infection induces a switch in macrophage functional programs.
- Motionless macrophages represent a permissive niche for bacterial persistence.
