PMID- 35027054 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20240321 IS - 1741-7007 (Electronic) IS - 1741-7007 (Linking) VI - 20 IP - 1 DP - 2022 Jan 14 TI - Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions. PG - 14 LID - 10.1186/s12915-021-01217-8 [doi] LID - 14 AB - 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. CI - (c) 2021. The Author(s). FAU - Meek, Stephen AU - Meek S AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. stephen.meek@roslin.ed.ac.uk. FAU - Watson, Tom AU - Watson T AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Eory, Lel AU - Eory L AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - McFarlane, Gus AU - McFarlane G AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Wynne, Felicity J AU - Wynne FJ AD - Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK. FAU - McCleary, Stephen AU - McCleary S AD - Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK. FAU - Dunn, Laura E M AU - Dunn LEM AD - The Pirbright Institute, Pirbright, Surrey, UK. FAU - Charlton, Emily M AU - Charlton EM AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Craig, Chloe AU - Craig C AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Shih, Barbara AU - Shih B AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Regan, Tim AU - Regan T AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Taylor, Ryan AU - Taylor R AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Sutherland, Linda AU - Sutherland L AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Gossner, Anton AU - Gossner A AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Chintoan-Uta, Cosmin AU - Chintoan-Uta C AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Fletcher, Sarah AU - Fletcher S AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Beard, Philippa M AU - Beard PM AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. AD - The Pirbright Institute, Pirbright, Surrey, UK. FAU - Hassan, Musa A AU - Hassan MA AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Grey, Finn AU - Grey F AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Hope, Jayne C AU - Hope JC AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Stevens, Mark P AU - Stevens MP AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Nowak-Imialek, Monika AU - Nowak-Imialek M AD - First Department of Medicine, Cardiology, Klinikum rechts der Isar - Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany. FAU - Niemann, Heiner AU - Niemann H AD - Gastroenterology, Hepatology and Endocrinology Department, Hannover Medical School, Carl Neuberg Str 1, 30625, Hannover, Germany. FAU - Ross, Pablo J AU - Ross PJ AD - Department of Animal Science, University of California, 450 Bioletti Way, Davis, CA, 95616, USA. FAU - Tait-Burkard, Christine AU - Tait-Burkard C AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Brown, Sarah M AU - Brown SM AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Lefevre, Lucas AU - Lefevre L AD - UK Dementia Research Institute, The University of Edinburgh, Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. FAU - Thomson, Gerard AU - Thomson G AD - Centre for Clinical Brain Sciences, University of Edinburgh, Department of Clinical Neurosciences, NHS Lothian, Edinburgh, UK. FAU - McColl, Barry W AU - McColl BW AD - UK Dementia Research Institute, The University of Edinburgh, Edinburgh Medical School, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. AD - Centre for Discovery Brain Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. FAU - Lawrence, Alistair B AU - Lawrence AB AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. AD - Scotland's Rural College (SRUC), West Mains Road, Edinburgh, EH9 3RG, UK. FAU - Archibald, Alan L AU - Archibald AL AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. FAU - Steinbach, Falko AU - Steinbach F AD - Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK. FAU - Crooke, Helen R AU - Crooke HR AD - Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK. FAU - Gao, Xuefei AU - Gao X AD - Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. FAU - Liu, Pentao AU - Liu P AD - The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. AD - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, Stem Cell and Regenerative Medicine, The University of Hong Kong, Hong Kong, China. AD - Centre for Translational Stem Cell Biology, Science Park, Hong Kong, China. FAU - Burdon, Tom AU - Burdon T AUID- ORCID: 0000-0001-6613-0519 AD - The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK. tom.burdon@roslin.ed.ac.uk. LA - eng GR - BB/P013732/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BBS/E/D/10002070/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/S02008X/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220114 PL - England TA - BMC Biol JT - BMC biology JID - 101190720 SB - IM MH - *African Swine Fever Virus/genetics MH - Animals MH - *Communicable Diseases MH - Host-Pathogen Interactions/genetics MH - Macrophages MH - Stem Cells MH - Swine PMC - PMC8759257 OTO - NOTNLM OT - ASFV OT - CRISPR OT - Macrophage OT - PRRSV OT - Pig OT - Pluripotent stem cell OT - gene editing COIS- The authors declare that they have no competing interests. EDAT- 2022/01/15 06:00 MHDA- 2022/04/15 06:00 PMCR- 2022/01/14 CRDT- 2022/01/14 05:31 PHST- 2021/09/28 00:00 [received] PHST- 2021/12/16 00:00 [accepted] PHST- 2022/01/14 05:31 [entrez] PHST- 2022/01/15 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] PHST- 2022/01/14 00:00 [pmc-release] AID - 10.1186/s12915-021-01217-8 [pii] AID - 1217 [pii] AID - 10.1186/s12915-021-01217-8 [doi] PST - epublish SO - BMC Biol. 2022 Jan 14;20(1):14. doi: 10.1186/s12915-021-01217-8.