TY - UNPB
T1 - Stem cell-derived macrophages as a new platform for studying host-pathogen interactions in livestock
AU - Meek, Stephen
AU - Watson, Tom
AU - Eory, Lel
AU - McFarlane, Gus
AU - Wynne, Felicity J.
AU - McCleary, Stephen
AU - Dunn, Laura E.M.
AU - Charlton, Emily
AU - Criag, Chloe
AU - Shih, Barbara
AU - Regan, Tim
AU - Taylor, Ryan
AU - Sutherland, Linda
AU - Gossner, Anton
AU - Chintoan-Uta, Cosmin
AU - Fletcher, Sarah
AU - Beard, Pip
AU - Hassan, Musa
AU - Grey, Finn
AU - Hope, Jayne
AU - Stevens, Mark
AU - Nowak-Imialek, Monika
AU - Niemann, Heiner
AU - Ross, Pablo J.
AU - Tait-Burkard, Christine
AU - Brown, Sarah
AU - Lefevre, Lucas
AU - Thomson, Gerard
AU - McColl, Barry W
AU - Lawrence, A B
AU - Archibald, Alan
AU - Steinbach, Falko
AU - Crooke , Helen R.
AU - Gao, Xuefei
AU - Liu, Pentao
AU - Burdon, Tom
PY - 2022/1/10
Y1 - 2022/1/10
N2 - 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.
AB - 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.
U2 - 10.1101/2021.09.10.459580
DO - 10.1101/2021.09.10.459580
M3 - Working paper
BT - Stem cell-derived macrophages as a new platform for studying host-pathogen interactions in livestock
PB - bioRxiv, at Cold Spring Harbor Laboratory
ER -