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Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions.
Meek, Stephen; Watson, Tom; Eory, Lel; McFarlane, Gus; Wynne, Felicity J; McCleary, Stephen; Dunn, Laura E M; Charlton, Emily M; Craig, Chloe; Shih, Barbara; Regan, Tim; Taylor, Ryan; Sutherland, Linda; Gossner, Anton; Chintoan-Uta, Cosmin; Fletcher, Sarah; Beard, Philippa M; Hassan, Musa A; Grey, Finn; Hope, Jayne C; Stevens, Mark P; Nowak-Imialek, Monika; Niemann, Heiner; Ross, Pablo J; Tait-Burkard, Christine; Brown, Sarah M; Lefevre, Lucas; Thomson, Gerard; McColl, Barry W; Lawrence, Alistair B; Archibald, Alan L; Steinbach, Falko; Crooke, Helen R; Gao, Xuefei; Liu, Pentao; Burdon, Tom.
Afiliación
  • Meek S; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. stephen.meek@roslin.ed.ac.uk.
  • Watson T; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Eory L; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • McFarlane G; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Wynne FJ; Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK.
  • McCleary S; Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK.
  • Dunn LEM; The Pirbright Institute, Pirbright, Surrey, UK.
  • Charlton EM; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Craig C; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Shih B; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Regan T; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Taylor R; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Sutherland L; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Gossner A; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Chintoan-Uta C; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Fletcher S; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Beard PM; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Hassan MA; The Pirbright Institute, Pirbright, Surrey, UK.
  • Grey F; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Hope JC; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Stevens MP; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Nowak-Imialek M; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Niemann H; First Department of Medicine, Cardiology, Klinikum rechts der Isar - Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany.
  • Ross PJ; Gastroenterology, Hepatology and Endocrinology Department, Hannover Medical School, Carl Neuberg Str 1, 30625, Hannover, Germany.
  • Tait-Burkard C; Department of Animal Science, University of California, 450 Bioletti Way, Davis, CA, 95616, USA.
  • Brown SM; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Lefevre L; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Thomson G; UK Dementia Research Institute, The University of Edinburgh, Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
  • McColl BW; Centre for Clinical Brain Sciences, University of Edinburgh, Department of Clinical Neurosciences, NHS Lothian, Edinburgh, UK.
  • Lawrence AB; UK Dementia Research Institute, The University of Edinburgh, Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
  • Archibald AL; Centre for Discovery Brain Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
  • Steinbach F; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Crooke HR; Scotland's Rural College (SRUC), West Mains Road, Edinburgh, EH9 3RG, UK.
  • Gao X; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
  • Liu P; Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK.
  • Burdon T; Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK.
BMC Biol ; 20(1): 14, 2022 01 14.
Article en En | MEDLINE | ID: mdl-35027054
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Transmisibles / Virus de la Fiebre Porcina Africana Aspecto: Ethics Límite: Animals Idioma: En Revista: BMC Biol Asunto de la revista: BIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Transmisibles / Virus de la Fiebre Porcina Africana Aspecto: Ethics Límite: Animals Idioma: En Revista: BMC Biol Asunto de la revista: BIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido