title: BCG-induced trained immunity in NK cells: Role for non-specific protection to infection.
abstract: Adaptive features of innate immunity, also termed 'trained immunity', have recently been shown to characterize monocytes of BCG vaccinated healthy volunteers. Trained immunity leads to increased cytokine production in response to non-related pathogens via epigenetic reprogramming of monocytes. Recently, memory-like properties were also observed in NK cells during viral infections, but it is unknown if memory properties of NK cells contribute to trained immunity due to BCG vaccination. BCG vaccination of healthy volunteers increased proinflammatory cytokine production following ex vivo stimulation of NK cells with mycobacteria and other unrelated pathogens up until at least three months after vaccination. In addition, in a murine model of disseminated candidiasis, BCG vaccination led to an increased survival in SCID mice, which was partially dependent on NK cells. These findings suggest that NK cells may contribute to the non-specific (heterologous) beneficial effects of BCG vaccination.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands. Electronic address: johanneke.kleinnijenhuis@radboudumc.nl.
authors.forename: Johanneke
authors.initials: J
authors.lastname: Kleinnijenhuis
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: Quintin
authors.affiliation: Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Preijers
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Cor
authors.initials: C
authors.lastname: Jacobs
authors.affiliation: Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology / Q000517:prevention & control; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D001500:BCG Vaccine; D016207:Cytokines; D018836:Inflammation Mediators; D007371:Interferon-gamma
keywords: BCG; Innate immunity; Trained immunity; Vaccination