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

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

Research output: Working paper

Abstract

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. We explored how pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages from livestock. Porcine and bovine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages. Pig PSCdMs were productively infected by 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, Pig PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied in parental stem cells, or directly by lentiviral vector transduction. PSCs and differentiated derivatives therefore provide a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in livestock.
Original languageEnglish
PublisherbioRxiv, at Cold Spring Harbor Laboratory
DOIs
Publication statusE-pub ahead of print - 10 Sep 2021

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