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Updated: Apr 13, 2026
High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Induced pluripotent stem cell derived macrophages as a cellular system to study salmonella and other pathogens
Christine Hale1, Amy Yeung1, David Goulding1
1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Abstract:
A number of pathogens, including several human-restricted organisms, persist and replicate within macrophages (Mφs) as a key step in pathogenesis. The mechanisms underpinning such host-restricted intracellular adaptations are poorly understood, in part, due to a lack of appropriate model systems. Here we explore the potential of human induced pluripotent stem cell derived macrophages (iPSDMs) to study such pathogen interactions. We show iPSDMs express a panel of established Mφ-specific markers, produce cytokines, and polarise into classical and alternative activation states in response to IFN-γ and IL-4 stimulation, respectively. iPSDMs also efficiently phagocytosed inactivated bacterial particles as well as live Salmonella Typhi and S. Typhimurium and were able to kill these pathogens. We conclude that iPSDMs can support productive Salmonella infection and propose this as a flexible system to study host/pathogen interactions. Furthermore, iPSDMs can provide a flexible and practical cellular platform for assessing host responses in multiple genetic backgrounds.
Insights
Human induced pluripotent stem cell-derived macrophages (iPSDMs) offer a novel model for studying pathogen interactions. These iPSDMs effectively model Salmonella infection, aiding research into host-pathogen dynamics.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Pathogens, including human-restricted organisms, replicate within macrophages (Mφs) during infection.
- Understanding host-pathogen interactions is crucial but limited by a lack of suitable model systems.
Purpose of the Study:
- To evaluate human induced pluripotent stem cell-derived macrophages (iPSDMs) as a model for studying pathogen interactions.
- To investigate the utility of iPSDMs in modeling Salmonella infections.
Main Methods:
- Characterization of iPSDMs for Mφ-specific markers and cytokine production.
- Assessment of iPSDMs' polarization in response to IFN-γ and IL-4.
- Evaluation of iPSDMs' phagocytic and killing capabilities against bacterial particles and live Salmonella.
Main Results:
- iPSDMs expressed key Mφ markers and produced cytokines.
- iPSDMs demonstrated functional polarization upon stimulation.
- iPSDMs efficiently phagocytosed and killed Salmonella Typhi and S. Typhimurium.
Conclusions:
- iPSDMs serve as a viable model for productive Salmonella infection.
- This system offers a flexible platform for studying host-pathogen interactions and host responses across diverse genetic backgrounds.
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