Cell-Based Models for Infection and Immunity

Stem cell-derived macrophage platform provides an ethical and scalable model to investigate host–pathogen interactions

Infectious diseases pose a major challenge to human and animal health, particularly in livestock where viral outbreaks cause significant economic and welfare losses. Understanding how pathogens interact with immune cells is vital for developing new interventions. Traditionally, this work has relied on primary macrophages from animals, which are limited in number, variable in quality, and raise ethical concerns. To overcome these barriers, researchers at the Engineering Biology Hub developed methods to generate macrophages from porcine pluripotent stem cells, creating a scalable and renewable cell-based model.

Pig PSC Macs Tox
Porcine PSC-derived macrophages infected with Toxoplasma gondii (Image provided by the Burdon Lab).

The Breakthrough: Stem Cell–Derived Macrophages

Macrophages are frontline immune cells that engulf and destroy invading pathogens. By harnessing induced pluripotent stem cell (iPSC) technology, functional macrophages were generated in vitro. These cells exhibit all the hallmarks of their primary counterparts, including surface markers, phagocytic activity, and the ability to mount immune responses. Crucially, they can be produced in large numbers and from genetically defined backgrounds, making them highly versatile for research.

The iPSC-derived macrophages (PSCdMs) have been used to model viral, bacterial, and parasitic infections. PSCdMs have been shown to be susceptible to infection by key swine pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV). Both of which have devastating impacts on livestock. They also support studies of bacterial and protozoan infections, such as Salmonella Typhimurium and Toxoplasma gondii.

 

Scaling Impact: From Lab to Application

By combining expertise in stem cell biology, immunology, and genetic engineering, the Roslin Institute and the Engineering Biology Hub are equipping researchers worldwide with an innovative, ethical platform to accelerate discoveries in infectious disease and drive the development of next-generation interventions.

Bovine Macs IL10 KO
Engineered bovine stem cell–derived macrophages. Representative image of IL-10 knock-out bovine stem cell–derived macrophages following infection with Mycobacterium bovis. Image provided by the Burdon Lab, with contributions from Emily Randall, Stephen Meek, Amy Findlay, and Kirsty Jensen.

PSC-derived macrophages unlock opportunities to:

  • Reduce animal use: Provide a renewable, ethical alternative to animal-derived macrophages, lowering reliance on animals in research.
  • Enable reproducibility at scale: Support controlled, standardised experiments on host–pathogen interactions.
  • Advance functional genomics: Serve as a platform for testing gene function and regulation, underpinning gene-editing strategies to address disease susceptibility.
  • Demonstrate cross-species potential: Engineered bovine stem cell–derived macrophages (e.g., IL-10 knock-outs) enable studies of bovine tuberculosis (Mycobacterium bovis).
  • Human health: Can act as a cell model for human infection studies when primary immune cells are not readily available.

A Collaborative Effort 

This work, led by Dr Tom Burdon, brought together expertise in stem cell biology, immunology, and virology, supported by advanced cell culture and gene-editing infrastructure at the Roslin Institute. Infection studies were conducted in collaboration with the Animal and Plant Health Agency, and the Pirbright Institute, ensuring the highest standards of animal welfare and biosafety. This work was supported by funding from BBSRC, The Roslin Foundation and National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).

 

Key publications 

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