title: Natural killer cells are required for extramedullary hematopoiesis following murine cytomegalovirus infection.
abstract: The immune response against a variety of pathogens can lead to activation of blood formation at ectopic sites, a process termed extramedullary hematopoiesis (EMH). The underlying mechanisms of EMH have been enigmatic. Investigating splenic EMH in mice infected with murine cytomegalovirus (MCMV), we find that, while cells of the adaptive immune system were dispensable for EMH, natural killer (NK) cells were essential. EMH required recognition of infected cells via activating NK cell receptors Ly49H or NKG2D, and correspondingly, viral interference with NK cell recognition abolished EMH. Surprisingly, development of EMH was not induced by NK cell-derived cytokines but was dependent on perforin-mediated cytotoxicity in order to control virus spread. Spreading virus reduced the numbers of F4/80(+) macrophages that were crucial for inflammatory EMH. Hence, whereas MCMV suppresses inflammation-induced EMH, NK cells confine virus spread, thereby protecting extramedullary hematopoietic niches and facilitating EMH.
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-Universität, 80336 Munich, Germany. Electronic address: jordan@mvp.uni-muenchen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jordan
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ruzsics
authors.affiliation: Department for Histology and Embryology, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Mitrović
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, UNIV UM2, 13288 Marseille, France; INSERM, UMR1104, 13288 Marseille, France; CNRS, UMR7282, 13288 Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Baranek
authors.affiliation: Department for Histology and Embryology, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Jurica
authors.initials: J
authors.lastname: Arapović
authors.affiliation: Department for Histology and Embryology, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Astrid
authors.initials: A
authors.lastname: Krmpotić
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, UNIV UM2, 13288 Marseille, France; INSERM, UMR1104, 13288 Marseille, France; CNRS, UMR7282, 13288 Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, UNIV UM2, 13288 Marseille, France; INSERM, UMR1104, 13288 Marseille, France; CNRS, UMR7282, 13288 Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.affiliation: Department for Histology and Embryology, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjić
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Dölken
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Koszinowski
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006411:Hematopoiesis, Extramedullary; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology