title: Induced pluripotent stem cell derived macrophages as a cellular system to study salmonella and other pathogens.
abstract: A number of pathogens, including several human-restricted organisms, persist and replicate within macrophages (Mφs) as a key step in pathogenesis. The mechanisms underpinning such host-restricted intracellular adaptations are poorly understood, in part, due to a lack of appropriate model systems. Here we explore the potential of human induced pluripotent stem cell derived macrophages (iPSDMs) to study such pathogen interactions. We show iPSDMs express a panel of established Mφ-specific markers, produce cytokines, and polarise into classical and alternative activation states in response to IFN-γ and IL-4 stimulation, respectively. iPSDMs also efficiently phagocytosed inactivated bacterial particles as well as live Salmonella Typhi and S. Typhimurium and were able to kill these pathogens. We conclude that iPSDMs can support productive Salmonella infection and propose this as a flexible system to study host/pathogen interactions. Furthermore, iPSDMs can provide a flexible and practical cellular platform for assessing host responses in multiple genetic backgrounds.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Hale
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: Yeung
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Kaur
authors.initials: K
authors.lastname: Alasoo
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D058507:Host Specificity; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis; D012486:Salmonella typhimurium / Q000472:pathogenicity*
chemical_list: D016207:Cytokines