Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions

Stephen Meek*, Tom Watson, Lel Eory, Gus McFarlane, Felicity J. Wynne, Stephen McCleary, Laura E. M. Dunn, Emily M. Charlton, Chloe Craig, Barbara Shih, Tim Regan, Ryan Taylor, Linda Sutherland, Anton Gossner, Cosmin Chintoan-Uta, Sarah Fletcher, Philippa M. Beard, Musa A. Hassan, Finn Grey, Jayne C. HopeMark P. Stevens, Monika Nowak-Imialek, Heiner Niemann, Pablo J. Ross, Christine Tait-Burkard, Sarah M. Brown, Lucas Lefevre, Gerard Thomson, Barry W. McColl, Alistair B. Lawrence, Alan L. Archibald, Falko Steinbach, Helen R. Crooke, Xuefei Gao, Pentao Liu, Tom Burdon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases.

Results: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction.

Conclusions: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock.
Original languageEnglish
Article number14
JournalBMC Biology
Volume20
Issue number1
Early online date14 Jan 2022
DOIs
Publication statusFirst published - 14 Jan 2022

Keywords

  • Methodology Article
  • Pig
  • Pluripotent stem cell
  • Macrophage
  • PRRSV
  • ASFV
  • CRISPR
  • gene editing

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